Treatments using cryogenic ablation systems

ABSTRACT

Methods and apparatus for the treatment of a body cavity or lumen are described where a heated fluid and/or gas may be introduced through a catheter and into treatment area within the body contained between one or more inflatable/expandable members. The catheter may also have optional pressure and temperature sensing elements which may allow for control of the pressure and temperature within the treatment zone and also prevent the pressure from exceeding a pressure of the inflatable/expandable members to thereby contain the treatment area between these inflatable/expandable members. Optionally, a chilled, room temperature, or warmed fluid such as water may then be used to rapidly terminate the treatment session.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/900,916 filed May 23, 2013, which is a continuation-in-part of U.S.patent application Ser. No. 13/361,779 filed Jan. 30, 2012, which claimsthe benefit of priority to U.S. Prov. Pat. App. 61/462,328 filed Feb. 1,2011 and U.S. Prov. Pat. App. 61/571,123 filed Jun. 22, 2011, each ofwhich is incorporated herein by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates to medical devices. In particular, thepresent invention relates to methods and apparatus for therapeuticdevices capable of exposing areas of the body to elevated or decreasedtemperatures, in a highly controlled manner.

BACKGROUND OF THE INVENTION

In the last few decades, therapeutic intervention within a body cavityor lumen has developed rapidly with respect to delivery of energy viaradiofrequency ablation. While successful in several arenas,radiofrequency ablation has several major downsides, includingincomplete ablation, frequent lack of visualization during catheterinsertion, potential for overlap during treatment (with some areasreceiving twice as much energy as other areas), charring of tissues andrequirements for frequent debridement, frequent requirements foradditional doses of energy after debridement, and potential perforationof the body cavity or lumen due to the rigidity of the RF electrodes.

The current state of the art would benefit from minimally invasivedevices and methods which deliver thermal energy to a desired area orextract energy from a desired area, in a consistent, controlled mannerthat does not char or inadvertently freeze certain tissues or createexcessive risk of unwanted organ or lumen damage.

SUMMARY OF THE INVENTION

When bodily tissues are exposed to even slightly elevated temperatures(e.g., 42 degrees C. or greater), focal damage may occur. If the tissuesare exposed to temperatures greater than, e.g., 50 degrees C., for anextended period of time, tissue death will occur. The energy deliveredby RF can then be excessive while a more controlled treatment can beachieved with heated fluids and/or vapors.

Generally, devices for delivering controlled treatment may comprise asource for a heated liquid and/or gas, e.g., hot water/steam, one ormore pumps to deliver said hot water/steam, a catheter having one ormore lumens defined therethrough and also having one or more ports todeliver or circulate the heated liquid and/or gas, e.g., hot waterand/or vapor, to a controlled site in a controlled manner. The cathetermay also have optional pressure and temperature sensing elements. Theoptional pressure and temperature sensing elements may allow theoperator to monitor and/or control the pressure and temperature withinthe treatment zone and also prevent the pressure from becoming too high.The treatment site may be delineated by inflatable or expandable memberswhich are pressurized or expanded to a target pressure to form a sealwith the body cavity/lumen. The heated liquid and/or gas may then bedelivered to the area contained by the inflatable/expandable members ata pressure that is less than that of the inflatable/expandable membersthereby effectively containing the treatment area between theseinflatable/expandable members. Optionally, a chilled, room temperature,or warmed fluid such as water may then be used to rapidly terminate thetreatment session.

The catheter having the inflatable/expandable members and optionalpressure or temperature-sensing elements may be fitted within the lumenof an endoscope or other visualization device allowing the therapy to bedelivered under direct visualization. In addition to directvisualization, this advance allows the scope to function as an insulatorfor the treatment catheter, thereby preventing unwanted exposure of bodycavities/lumens to the elevated temperatures found in the heated liquidand/or gas coursing within the treatment catheter.

Generally, the heated liquid and/or gas may be heated to a temperatureof between, e.g., 50 and 100 degrees Celsius. Exposure to these lesselevated temperatures may allow for more controlled tissue damage andmay obviate issues typically associated with the higher energy forms oftreatment. It is understood and known in the art that the lower thetemperature, the longer the dwell/treatment time needed. One treatmentmodality may be to deliver the heated liquid and/or gas at a temperatureof, e.g., about 70 degrees C. for 5 minutes. Another modality may be totreat the tissue with the heated liquid and/or gas at a temperature of,e.g., 90 degree C. for 30 secs.

Among other features, the system may also include 1) the ability tothoroughly treat the treatment area due to the use of confiningballoon(s) and/or use of an umbrella-like seal and use of a pressurizedheated liquid and/or gas as the energy delivery medium, 2) the abilityto treat relatively large areas in a very controlled manner due to theadjustable relationship between the two treatment-area defininginflatable/expandable components (e.g. balloon(s) and/or anumbrella-like seal), 3) the ability to form a liquid and/or gas-tightseal between the balloon(s) (and/or an umbrella-like seal) due to thecatheter for the distal balloon traveling within the lumen of theproximal balloon catheter (avoidance of leakage around the cathetersthat the balloons can seal about), 4) the optional ability to monitorand control the pressure within the treatment area to ensure that thetreatment area is not exposed to excessive pressures and that thepressure in the treatment area is prohibited from exceeding a pressureof the treatment area defining balloons, 5) the ability to ablate to acontrolled depth in a reliable manner due to the lower energy and longerexposure times which allow the submucosa to cool itself with incomingblood flow, 6) the optional ability to fit within a working channel ofan endoscope so that the device need not be inserted in a blind manner,7) the ability to combine thermal or cooling therapy with delivery ofactive agents (e.g., anesthetic for pre-treatment of the target area ora chemotherapeutic for the treatment cancer or precancerous lesions,etc.), 8) the ability to fill the treatment defining area with fluid(e.g. cool, warm or room temperature fluid) capable of neutralizing thethermal or cooling energy in the treatment area in order to preventpotential damage caused by balloon rupture or seepage around the balloonand/or expandable member, 9) the ability to pre-chill (or pre-warm) thetreatment area so that the submucosal tissues can be protected againstthe elevated (or cooling) temperature to which the lumen or bodily organis being exposed, 10) the ability to adjust the treatment temperaturetime and/or temperature, 11) the ability to have modular, automated orsemi-automated components and controls for handling the cooling,heating, inflations, deflations, infusions and/or extractions, 12) theability to treat through the working channel of an endoscope oralongside an endoscope, 13) the ability to treat through a variety ofendoscopes, e.g. nasal, gastrointestinal, esophageal, etc., 14) theability to use off-the-shelf and/or disposable components to handle thefluid and pressure controls, or to use an automated or semi-automatedsystem.

Additionally, the system may also incorporate features that may allowfor efficacious therapy. For example, the system may utilize a sub-zerodegrees Celsius temperature fluid lavage. This cold lavage may allow formuch better control than charring and heating of the tissue and insteadmay provide a consistent depth of ablation in a manner that allows forrapid recovery and minimal post-operative pain (as opposed to heatingmethods). In addition, by using lavage of a liquid rather than cryogenicsprays (e.g., sprays which rely on the judgment of the user fordetermining time of spray application or spray location, etc.), thepotential for over-ablation may be avoided. Also, the relatively coldercryogenic sprays have been found, in many cases, to result in damage tothe endoscope while the higher temperatures possible with the systemdescribed herein (e.g., anywhere from −5 degrees Celsius to −90 degreesCelsius) is much less likely to damage the delivery equipment.

Secondly, the apparatus may utilize an umbrella-like element in thegastric space to allow for ablation of tissue regions, such as the loweresophageal sphincter at the gastroesophageal junction. This ablation isgenerally difficult to perform using balloon-based ablation technologiesdue to the expansion of the sphincter into the stomach. By utilizing anexpandable, umbrella-like structure to form a firm seal at this sitewhile allowing the ablation liquid and/or gas (heated or chilled) tocontact the entire gastroesophageal junction. In addition, aspring-loaded element or other external force mechanism may beincorporated to provide for steady pressure and a firm seal against thestomach lining.

The apparatus may also be utilized with or without a balloon in bodylumens or cavities that can be otherwise sealed. For example, ahypothermic fluid lavage of the uterus may be accomplished byintroducing a subzero (Celsius) fluid into the uterus via cannulation ofthe uterus with a tube or cannula. If the tube is of sufficientdiameter, backflow of the hypothermic lavage into the cervix and vaginamay be prevented without the need for a balloon to contain the fluid.Use of balloons may be avoided for this particular type of application.In utilizing a hypothermic lavage, a fluid may be used that remainsfluid even at subzero temperatures. This fluid may then circulated inthe lumen (with or without a balloon) in order achieve ablation.

In using a hypothermic liquid rather than a gas, a greater thermal loadcan be repeatedly extracted from the tissue under controlled physiologicconditions using a liquid beyond the thermal load which may be extractedusing a compressed gas. A liquid lavage, on the other hand, may becontrolled based on temperature and pressure to provide a repeatableeffect on the target organ. Compressed gas or other rapid coolingmechanisms, though, may be utilized in combination with this therapy inorder to chill a solution to subzero temperatures after introductioninto the body. In this variation, the biocompatible liquid capable ofretaining liquid characteristics in a subzero state, or “anti-freezesolution”, may be infused into the lumen or cavity after which thecooling probe may be introduced. Heat may be drawn from the anti-freezesolution until the desired hypothermic ablation temperature has beenachieved for the desired duration of time. Fluid may or may not becirculated during this process via a pump or agitating element withinthe catheter in order to improve distribution of the ablative fluid.

In yet another variation, the treatment fluid may function to expand theuterus for consistent ablation, function to distribute the cryoablativefreezing more evenly throughout the uterus, and potentially function toslow or prevent ice formation at the surface of the lumen or bodycavity. The apparatus may be used with, for example, lipophilic,hydrophilic or amphipathic solutions with the latter two being havingthe ability to remove any aqueous fluid from the surface of the targetcavity or lumen which may interfere with conduction of the heat from thetarget tissues into the cryoablative fluid.

Additionally and/or alternatively, the apparatus and methods describedherein may be used as an adjunct to other treatments, such as the HerOption® therapy (American Medical Systems, Minnetonka, Minn.), byutilizing a lavage of the target cavity or lumen such as the uterus withthe aqueous anti-freeze solution either prior to or during treatment inorder to provide superior transmission of cryoablation with otherexisting cryoprobes without creation of the insulating ice layer at thesurface. Moreover, lavage of the target lumen or cavity with abiocompatible antifreeze solution may be performed to improvetransmission of the cryoablative effect as an adjunct to any cryotherapytreatment anywhere in the body where applicable. As described herein,the cryoablative fluid may also be introduced and/or lavaged within thetarget lumen or body cavity within a balloon which may be expanded tocontact the walls of the lumen or body cavity. The cryoablativetreatment fluid may be actively lavaged in and out of the balloon and/ordeeply chilled by a cryoprobe within the balloon after introduction intothe body cavity or lumen. Moreover, the anti-freeze solution may alsocomprise various salts and/or other biocompatible molecules capable ofdriving the freezing temperature of the solution below, e.g., −10degrees Celsius. Additionally, the fluid may be capable of resistingfreezing even at a temperature of, e.g., −90 degrees Celsius. Acombination of salts, alcohols, glycols and/or other molecules may beused to provide this resistance to freezing in an aqueous solution.

In yet another variation, a cryoprobe with, e.g., a protective cageand/or a recirculator/fluid agitator, may be utilized to ensure that thehypothermic fluid is evenly distributed. The cage may be configured intovarious forms so long as it exposes the fluid to the surface of thecryoprobe while preventing direct contact of the cryoprobe with the wallof the lumen or cavity to be ablated (such as a uterus). A recirculatormay comprise, e.g., a stirring element at the tip of the cryoprobe, anintermittent or continuous flow system or other fluid movementmechanism.

In another variation, to facilitate the balloon expanding and conformingreadily against the tissue walls of the uterus, the balloon may beinflated with a gas or liquid. Alternatively, the balloon may be filledpartially or completely with a conductive material. Once the elongateshaft has been introduced through the cervix and into the uterus, thedistal opening of the shaft may be positioned distal to the internal osand balloon may be deployed either from within the shaft or from anexternal sheath. The balloon may be deployed and allowed to unfurl orunwrap within the uterus. The cooling probe may be introduced throughthe shaft and into the balloon interior (or introduced after insertionof the conductive elements).

The conductive elements may be introduced into the balloon interiorthrough an annular opening within the distal end of the shaft until theballoon is at least partially or completely filled with the elements.The conductive elements may generally comprise any number of thermallyconductive elements such as copper spheres or some other inert metalsuch as gold. These conductive elements may be atraumatic in shape andare small enough to fill the balloon interior and conform the balloonwalls against the uterine walls to ensure consistent contact with thetissue, e.g., about 20 ml in volume of the elements. The conductiveelements may also help to fill any air pockets which may formparticularly near the tapered portions of the balloon and insulate thetissue from the ablative effects of the cryoablative fluid. Forinstance, the conductive elements may be formed into spheres having adiameter of, e.g., 0.8 mm to 4 mm or larger. To ensure that thatconductive elements are fully and evenly dispersed throughout theballoon interior, the elements may be introduced through the shaft viaan ejector or push rod, auger, compressed air, etc. In particular, theconductive elements may fill the tapered portions of the balloon toensure that the balloon is positioned proximate to and in contact withthe uterine cornu to fully treat the interior of the uterus.

With the conductive elements placed within the balloon, the cryoablativefluid may be introduced within and through the balloon such that theconductive elements facilitate the thermal transfer from the contacteduterine walls. Once the cryoablative treatment has been completed, theconductive elements may be removed through the shaft via a vacuum forceor other mechanical or electromechanical mechanisms and the balloon,once emptied, may also be withdrawn from the uterus.

The cooling probe introduced into the interior of the balloon maycomprise a number of different configurations which facilitate theintroduction of the cryoablative fluid into the balloon. One suchvariation, the shaft may have one or more cooling members which projectfrom the distal end of the shaft at various angles. Another variation ofthe cooling probe may have a rotating base and spray member positionedupon the shaft. The spray member may have a surface which is meshed,latticed, perforated, etc. such that the cryoablative fluid introducedthrough the shaft may enter the rotating base and spray member where itmay be evenly dispersed through the spray member and into the interiorof the balloon for treatment.

The cooling probe positioned within the balloon may be variouslyconfigured and may include further variations. The cooling probeassembly may comprise an exhaust catheter having an atraumatic tip andan imaging instrument such as a hysteroscope positioned within. One ormore supporting members or inserts may be positioned throughout thelength of the lumen to provide structural support to the catheter and toprevent its collapse and a probe support (e.g., flat wire, ribbon, etc.)may extend through the catheter interior.

The probe support may be supported within the lumen via the inserts suchthat the probe support separates the lumen into a first channel and asecond channel where the cooling lumens may be positioned along theprobe support within the second channel while the first channel mayremain clear for the optional insertion of a hysteroscope. Because ofthe thickness of the probe support relative to its width, the probesupport may be flexed or curved in a single plane while remainingrelatively stiff in the plane transverse to the plane.

The probe may further include one or more cooling lumens which arepositioned along the probe support within the second channel. Becausethe cooling lumens are located along the second channel, as separated bythe probe support, one or more windows or openings may be defined alongthe length of the probe support to allow for the passage of anycryoablative fluid to proliferate through the entire lumen defined bythe catheter. The number of cooling lumens may also be varied to numbermore than three lumens terminating at different positions along theactive portion.

As the cryoablative fluid is introduced into and distributed throughoutthe catheter lumen, the exhaust catheter may also define one or moreopenings to allow for the cryoablative fluid to vent or exhaust from thecatheter interior and into the interior of the balloon.

One example for a treatment cycle using a two cycle process may includethe introduction of the cryoablative fluid for a treatment time of twominutes where the surrounding tissue is frozen. The fluid may bewithdrawn from the balloon and the tissue may be allowed to thaw over aperiod of five minutes. The cryoablative fluid may be then reintroducedand the tissue frozen again for a period of two minutes and the fluidmay then be withdrawn again to allow the tissue to thaw for a period offive minutes. The tissue may be visually inspected, e.g., via thehysteroscope, to check for ablation coverage. If the tissue has beensufficiently ablated, the assembly may be removed from the uterus,otherwise, the treatment cycle may be repeated as needed. In otheralternatives, a single cycle may be utilized or more than two cycles maybe utilized, as needed, to treat the tissue sufficiently. Furthermore,during the treatment cycle, a minimum pressure of, e.g., 40 to 80 mm Hg,may be optionally maintained by the cryogenic liquid or by a gas (e.g.,air, carbon dioxide, etc.) to keep the balloon and uterus open.

The balloon may be expanded within the uterus and particularly into theuterine cornu by an initial burst of gas or liquid. Other mechanisms mayalso be used to facilitate the balloon expansion. One variation mayutilize one or more supporting arms extending from a support which maybe deployed within the balloon. The supporting arms may be variouslyconfigured although they are shown in this example in a Y-configuration.Yet another variation may include the supporting arms incorporated intoelongate channels or pockets defined along the balloon itself.

Aside from the balloon itself and the use of balloons for obstructingthe os, internal os, and/or external os, balloons or inflatable linersmay also be used to insulate the cryogenic fluid during delivery intothe balloon to protect the surrounding tissue structures which are notto be ablated, such as the cervix.

In controlling the ablative treatments described above, the treatmentassembly may be integrated into a single cooling system containedentirely within the handle assembly or it may be separated intocomponents, as needed or desired. In either case, the cooling system maygenerally comprise a microcontroller for monitoring and/or controllingparameters such as cavity temperature, cavity pressure, exhaustpressure, etc.

A coolant reservoir, e.g., nitrous oxide canister, may be fluidlycoupled to the handle and/or elongate shaft via a coolant valve whichmay be optionally controlled by the microcontroller. The coolantreservoir may be in fluid communication with the cooling probe assemblyand with the interior of the balloon. Additionally, an exhaust lumen incommunication with the elongate probe and having a back pressure valvemay also include a pressure sensor where one or both of the backpressure sensor and/or valve may also be in communication with themicrocontroller.

BRIEF DESCRIPTION OF THE DRAWINGS

For the purposes of the drawings and preferred embodiments, applicationsto the esophagus and uterus will be shown. However, the apparatus andmethods may be applied to any body cavity/lumen which may be visualizedwith an endoscope or other visualization mechanism.

FIG. 1 shows an example of a device advanced through an endoscope, e.g.,a nasally or orally inserted scope.

FIG. 2 shows an example of a device advanced through the working channelof nasal endoscope.

FIG. 3 shows an example of a device attached to a logic controller.

FIG. 4 shows an example of a device placed through working channel ofnasal endoscope and deployed within an esophagus for treatment.

FIG. 5 shows an example of a device advanced alongside an endoscope.

FIGS. 6A to 6C show a device being introduced through an endoscope anddeployed for treatment within the esophagus.

FIGS. 7A to 7C show examples of a device introduced through an endoscopefor insertion within a bladder.

FIGS. 8A to 8C show examples of a device preparing the treatment areawith a pre-treatment lavage prior to treatment.

FIG. 9 shows an example of a distal occlude having an umbrella-likeshape deployed in proximity to a gastroesophageal junction fortreatment.

FIG. 10 shows another example of an endoscopic balloon sheath having adistal occluder expanded distal to gastroesophageal junction fortreatment.

FIG. 11 shows another example where the treatment fluid is introducedbetween the deployed balloons for treatment.

FIG. 12 shows another example of an adjustable size balloon device fortreatment of the esophagus.

FIGS. 13A and 13B show another example of a single balloon device forablation treatment within the uterus and/or endometrial lining.

FIGS. 14A and 14B show yet another example of conductive lattice/cagedeployed for cryoablative treatment.

FIG. 15 shows another example of an external cervical os occludingdevice.

FIG. 16 shows another example of an internal cervical os occludingdevice.

FIGS. 17A and 17B show another example of a device having a deployablelow-pressure conforming balloon used for cryogenic treatment of theuterus.

FIGS. 18A to 18D show another example of a conforming balloon which mayalso be filled partially or completely with a conductive material forcryoablative treatment.

FIG. 19 shows another example of a cooling probe having one or morecooling members projecting from the distal end of a shaft.

FIG. 20 shows another example of a cooling probe having a rotatable baseand spray member.

FIG. 21A shows a side view of an integrated treatment assembly.

FIG. 21B shows an example of the assembly advanced through the cervixand into the uterus where the sheath may be retracted via the handleassembly to deploy the balloon.

FIG. 21C shows a perspective view of a cryoablation assembly having ahandle assembly which may integrate the electronics and pump assemblywithin the handle itself.

FIG. 21D shows the handle assembly in a perspective exploded viewillustrating some of the components which may be integrated within thehandle.

FIG. 21E shows an example of the system operation during a pre-treatmentpuff up process.

FIG. 21F shows an example of the system operation during a treatmentprocess.

FIG. 21G shows an example of the system operation during a thawing andventing process.

FIG. 22A shows a side view of a system which allows for adjustablysetting a length of the balloon along the shaft.

FIG. 22B shows a side view of the balloon everted within the shaft lumenfor delivery.

FIGS. 23A and 23B show perspective and side views, respectively, ofanother example of a cooling probe assembly having a flat wireintegrated through the probe.

FIG. 24 shows a perspective view of the cooling probe assembly with oneor more openings defined along the probe assembly.

FIGS. 25A and 25B show end views of a cross-section of the cooling probeand the distal end of the probe.

FIGS. 26A to 26L show perspective views of various tubular members whichmay be used for the cooling probe assembly.

FIGS. 27A and 27B show perspective views of a cooling probe assemblyutilizing one or more discrete ring members linearly coupled to oneanother.

FIGS. 28A and 28B show cross-sectional end views of another variation ofa cooling probe assembly coupled via a covering and/or insert members.

FIG. 29 shows a perspective view of another variation of a cooling probeassembly having one or more insert members coupled along a wound springbody.

FIGS. 30A and 30B show cross-sectional side views of another variationof insert members supported along a spring body.

FIG. 31 shows a detail side view of one variation of a pivotable coolinglumen body.

FIG. 32 shows a side view of another variation of one or more insertmembers having an integrated covering.

FIG. 33 shows a side view of yet another variation of one or more insertmembers having a slidable joint attached.

FIG. 34 shows a side view of another variation of a spring body havingone or more cooling lumens attached directly to the spring.

FIG. 35 shows a side view of another variation of a spring body havingthe one or more insert members.

FIG. 36 shows a side view of another variation of a spring body havingthe one or more cooling lumens and a secondary lumen.

FIG. 37 show cross-sectional end views of variations of the secondarylumen.

FIGS. 38A and 38B show perspective views of another variation of thecooling probe utilizing a main delivery line and at least two sidedelivery lines.

FIG. 38C shows a detail view of the side delivery line having anadjustable mandrel slidably positioned within.

FIG. 39 shows a cross-sectional side view of another variation of thecooling probe assembly where the main delivery line and side deliverylines are in fluid communication through a common chamber.

FIGS. 40A and 40B show cross-sectional end views of variations of theexhaust lumen and the respective cooling lumens.

FIG. 41 shows a cross-sectional side view of another variation of acooling probe assembly having a single introduction line and a singledelivery line.

FIG. 42 shows a cross-sectional side view of a cooling probe assemblyinserted within a balloon within the uterus.

FIGS. 43A and 43B show side views of various examples of side deliverylines having the openings aligned in different directions.

FIG. 44 shows a side view of a cooling probe variation having a skivedwindow for facilitating visualization.

FIG. 45 shows a side view of an example of a balloon having one or moresupporting arms extendable within the balloon.

FIG. 46 shows a side view of another example of a balloon having one ormore supporting arms attached to the cooling probe assembly.

FIG. 47 shows a side view of another example of a balloon having one ormore supporting arms also defining one or more openings for deliveringthe cryoablative fluid.

FIG. 48 shows a side view of yet another example of a balloon having theone or more supporting arms positioned within elongate channels alongthe interior of the balloon.

FIGS. 49A and 49B show cross-sectional side views of yet anothervariation of a cooling probe which utilizes a single infusion line incombination with a translatable delivery line.

FIGS. 50A and 50B show top and perspective views of the expanded linerwith four pairs of the open delivery ports exposed in apposed direction.

FIG. 50C shows a perspective view of an expanded liner with additionalopen delivery ports exposed along an anterior portion of the liner.

FIG. 51A shows one variation of a probe incorporating a transmitter tofacilitate probe positioning within the liner.

FIG. 51B shows another variation of a probe incorporating one or moretransmitters to monitor tissue cavity expansion.

FIGS. 52A and 52B show a schematic illustration of a system utilizing a5-port, 2 position, 4-way valve.

FIGS. 53A to 53C show a schematic illustration of a system utilizing anon-reversible pump for both inflation and deflation.

FIGS. 54A and 54B show top and perspective views of a liner illustratingits curved features when flattened and expanded and then deployed in aconsistent manner.

FIG. 54C shows a perspective view of a liner which may be pleated tofold and collapse in a consistent manner.

FIGS. 55A and 55B show side and top views of a probe which is configuredto flex in the anterior and posterior directions.

FIG. 55C shows a perspective view of a probe having multiple probesections (e.g., four sections in this variation) separated by H-slots.

FIGS. 56A and 56B show perspective and detail cross-sectional views of asheath assembly.

FIG. 56C shows a cross-sectional view of a sheath assembly incorporatinga sensor, e.g., temperature sensor.

FIG. 57 shows one variation of a sheath bearing tube slidingly passingthrough a sheath bearing assembly and then attached to a slider baseblock assembly positioned within the handle assembly.

FIG. 58 shows a detail perspective view of the connection between thesheath bearing tube and slider base block assembly.

FIGS. 59A and 59B illustrate how the slider base block assembly may beadvanced distally or proximally relative to the handle assembly toexpose the probe length.

FIG. 60 shows a perspective view of one or more optional pressuresensing lines incorporated along the probe.

FIG. 61 shows a side view of an example of an inflatable liner orballoon located along the outside distal surface of the sheath.

FIG. 62 shows a side view of another example of an inflatable liner orballoon located along the inside distal surface of sheath.

FIG. 63 shows a side view of another example where expandable foam maybe deployed via the outer sheath.

FIG. 64 shows a side view of another example where a heating element maybe located along the inner or outer surface of the elongate shaft.

FIG. 65 shows a side view of another example where a ring balloon may beinflated along either the sheath or shaft to either insulate thesurrounding cervical tissue or to ensure secure placement of the shaftand/or balloon during treatment.

FIG. 66 shows a cross-sectional side view of another variation where theouter sheath may be formed as an inflatable structure.

FIGS. 67A and 67B show side views of variations of an outer sheathhaving a reconfigurable distal end.

FIG. 68 shows a side view of another variation of a balloon positionedalong an outer surface of the outer sheath.

FIG. 69 shows a cross-sectional side view of one variation of adual-sheath design.

FIGS. 70A and 70B show cross-sectional detail views of the sealingbetween the inner and outer sheaths.

FIG. 71 shows a partial cross-sectional side view of another dual-sheathvariation having an expandable balloon contained between the sheaths.

FIG. 72 shows a side view of another variation of a sheath having areinforced structure.

FIG. 73 shows a cross-sectional side view of another variation of anouter sheath having an adjustable balloon member.

FIGS. 74A and 74B show cross-sectional side views of another variationof an outer sheath having a reconfigurable distal end.

FIG. 75 shows a cross-sectional side view of the reconfigurable distalend having one or more lubricious surfaces.

FIG. 76 shows a partial cross-sectional side view of another variationwhere the reconfigurable distal end may be attached as a separatecomponent.

FIG. 77 shows a cross-sectional side view of another variation where adistal end of the cooling probe has a tapered distal end.

FIG. 78 shows a side view of another variation of an outer sheath havinga radially expandable portion.

FIGS. 79A and 79B show cross-sectional side views of variations of thelocking mechanism for the expandable portion.

FIGS. 80A and 80B show cross-sectional side views of an illustrativeexample of an overcenter linkage mechanism.

FIG. 81 shows a cross-sectional side view of another variation of anouter sheath having one or more distal cam members.

FIG. 82 shows a cross-sectional side view of the one or more cam membersdeployed in their expanded configuration and secured against thecervical tissue.

FIG. 83 shows a cross-sectional side view of another variation where thecammed distal end positioned on a tapered outer sheath.

FIG. 84 shows a side view of an example of how the outer sheath may beinitially deployed and secured and the cooling probe assembly advancedseparately.

FIG. 85 shows a side view of another variation where the outer sheath isconfigured as a corrugated structure.

FIG. 86 shows a partial cross-sectional side view of another variationof the outer sheath having an inflatable balloon along an inner surface.

FIG. 87 shows a partial cross-sectional side view of another variationof the outer sheath having an inflatable balloon along an outer surface.

FIG. 88A to 88D show cross-sectional end view of variations of the outersheath having an integrated feature to provide further insulation to thesurrounding tissue.

FIG. 89 shows an exemplary schematic illustration of the treatmentassembly integrated into a single cooling system.

FIGS. 90A and 90B show a device for closing the exhaust flow path tofacilitate a liner integrity check and to also increase the pressurewithin the uterine cavity.

FIGS. 91A and 91B show a schematic side view of a flapper valve and atop view of a gasket within the flapper valve for maintaining exhaustback pressure within the system.

FIGS. 91C to 91E show schematic side views illustrating an example ofthe flapper valve operation.

FIGS. 92A and 92B show schematic side views of another variation of theflapper valve.

FIG. 93 shows how the various algorithms may be programmed into theprocessor or microcontroller and how they may functionally interact withone another.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 shows a perspective view of one example of the treatment assembly10 positioned within a working channel 14 of an endoscope 12 (e.g.,orally or nasally insertable scope). In this example, the treatmentdevice 16 itself may utilize a first catheter 18 having an inflatable orexpandable balloon member 22 and a second catheter 20 that may slidefreely with respect to the first catheter 18 and also having aninflatable balloon member 24 at its distal end. The first catheter 18 aswell as second catheter 20 may have a liquid and/or gas tight seal 30formed at the proximal end of the catheters. The inflatable and/orexpandable members 22, 24 (shown in this example as inflated balloons)may be pressurized to effectively and safely occlude the lumen. Theballoons may be filled with chilled or room temperature fluid to preventpossible damage caused by balloon rupture or seepage around the balloon.Pressure within the inflatable or expandable balloon members may also bemonitored to ensure that a tight seal has been formed within the lumenor body cavity.

Additionally, the liquid may be introduced into the treatment areathrough a liquid and/or gas port 28 and into the lumen of the catheterwhich terminates with the proximal balloon 22 and leaves the catheterthrough perforations or holes 32 within the second catheter 20 whichterminates in the distal balloon 24, although this flow path may easilybe reversed if necessary. Alternatively, one or more ports can bedesigned into the lumen between the distal 24 and proximal 22 balloons,such that the heated or cooling fluid exits one or more ports 32 in thelumens near the distal balloon 24, and is then evacuated in a port orports designed within the lumen of the first catheter 18 nearest theproximal balloon 22. In this variation, the endoscope 12 may insulatethe catheters allowing the catheters to be much smaller than would beotherwise possible and allowing it to fit within the working channel 14of a standard endoscope 12. One or more pressure sensors may be used todetect both inflation pressures of the balloons and/or the pressure seenby the body cavity/lumen that is exposed to the treatment liquid/vapor.In the manner, liquid/vapor flow may be controlled by the pressuresensing elements within the body cavity/lumen to ensure that safepressures are never exceeded. Manual controls may be used for creationand/or maintenance of these pressures (e.g. syringes with stopcocks) orautomated and/or semi-automated systems can be used as well (e.g. pumpswith PID loops and pressure sensing interconnectivity. Although theliquid and/or gas for tissue treatment may be heated or chilled prior tointroduction into the treatment area in contact with the tissue, theliquid and/or gas may alternatively be heated or chilled afterintroduction into the treatment area and already in contact with thetissue.

FIG. 2 shows an example where the second catheter 20 and distal balloonmember 24 is slidable relative to the proximal balloon 22. This examplesillustrates the endoscope inserted through the nasal cavity and advancedthrough the esophagus ES where the catheters 18, 20 may comprise singleor multi-lumen catheters having inflation lumens for the distal 24 andproximal 22 inflatable/expandable elements, infusion port and extractionport. At least one of the catheters may be fitted with either a pressuretransducer 42 or a lumen to carry the pressure signal from the treatmentarea back to the controller or dial gauge. Pressure sensing may beaccomplished through a small, air capsule proximal to the distal balloon24, but within the treatment area. Both of the balloons 22, 24 may beinflated along the esophagus ES in the proximity to the gastroesophagealjunction GJ proximal to the stomach ST to create a treatment space 40which encompasses the tissue region to be treated.

In an alternative embodiment, an extraction lumen may be omitted as apreset dose of heated liquid and/or gas may be delivered, allowed todwell and then either extracted through the same lumen or renderedharmless with the infusion of cold fluid. This treatment algorithm wouldprovide an even simpler therapy and would rely on the exclusion of acertain area and exposure of that area to a liquid or vapor with thedesired energy. Infusion of the liquid or vapor may be controlled toensure that the treatment area is not exposed to excessive temperatures.

FIG. 3 shows another example where the treatment assembly 10 may be incommunication with a controller 50, such as a logic controller.Controller 50 may control certain parameters such as infusion pressure54 of the fluid as well as fluid temperature 56 and it may be coupled tothe assembly by one or more cables 52. The pressure in the treatmentarea, the elapsed time, the temperature of the fluid, and the extractionrate may also be monitored and controlled.

FIG. 4 shows a detail view of the treatment area 40 defined, in thiscase, by two balloons 22, 24. The first catheter 18 may open into thelumen just after the proximal balloon 22 and this catheter 18 may beinserted along with or prior to insertion of the second catheter 20. Thefirst catheter 18 internal diameter is greater than the outer diameterof the second catheter allowing for liquid (and/or vapor) to be infusedor extracted around the outer diameter of the second catheter 20. Thesecond catheter 20 a first lumen for balloon inflation and a secondlumen for evacuating the treatment region 40. With the balloons inflatedinto contact against the esophagus ES, the treatment area 40 mayencompass the tissue region to be treated, e.g., a lesion 60 such asBarrett's esophagus or esophageal cancer lesion and the distal end ofthe endoscope 12 may be positioned into close proximity to proximalballoon 22 and the treating liquid and/or gas 66 may be infused throughthe annular lumen 70 defined through first catheter 18 and betweensecond catheter 20 such that the fluid 66 may enter through opening 62into the treatment region 40 while contained by the balloons. Oncetreatment has been completed, the fluid may be evacuated 68 through oneor more openings 64 located along the second catheter 20 proximal todistal balloon 24 and proximally through the second catheter 20 throughthe evacuation lumen 72. As previously mentioned, a pressure sensor 42(e.g., pressure measuring air capsule) may be positioned along eitherthe first 18 and/or second 20 catheter for sensing the variousparameters. Additionally, the treatment liquid and/or gas may includeany number of liquids, vapors, or other chemically active (e.g.,chemotherapeutic) or inactive compounds for additional treatments to thetissue.

In the event that the treatment is provided by a simple timed dwell, theextraction 72 and infusion 70 lumens may not both be utilized. Thepressure sensing element 42 (solid-state, piezoelectric, or othermethod) may be located on either the first or second catheters and thesecond catheter and may comprise a simple slidable balloon. A pressuresensor for the treatment may be omitted so long as the pressure can becontrolled by other mechanisms, e.g., a check valve or a simple gravityfluid column. An active pressure measurement, though, may ensure thatsafe pressures are not being exceeded.

The second catheter 20 may fit easily within the first catheter 18 andmay be slid inside the first catheter 18 until its distal balloon 24 isdistal to the first balloon 22. The distal balloon 24 may then beinflated just beyond the distal portion of the treatment area 40 and theendoscope 12 may be pulled back. The most proximal extent of the lesion60 may then be identified and the proximal balloon 22 may be inflatedproximal to this area. Once the treatment area 40 has been enclosed(which may be verified by infusing liquid 66 and/or vapor undervisualization and observing the seal around the balloon, balloons and/orexpandable member) the lumen or body cavity may then be filled with thetreatment liquid and/or vapor to a safe pressure. The liquid and/orvapor may also contain active agents (e.g. chemotherapeutic and/oranesthetic agents) and comprise more than simply an inactive liquidand/or vapor. Options would be for the active agents to be deliveredprior to, during and/or post treatment of the heating (or cooling)liquid and/or vapor.

As the treatment assembly 16 does not contain the treatment liquid orvapor within a balloon(s) or expandable member and allows it to freelyflow over the treatment area, the therapy may be applied consistentlyleaving no areas left untreated (as is frequently seen with ballooninfusion-based or RF therapies). Additionally, treatment may beaccomplished with a heated liquid (rather than a high energy electrodeor excessively hot vapor) or a more controlled treatment can be achievedthrough the use of a relatively cooler liquid with a longer treatmenttime. In addition, the esophagus ES is a fluid transport type organ(lumen) and may be more compatible to fluid based therapies than withRF-based therapies. It is also believed that the safety margin of suchtreatments may be better than with an RF-based therapy.

FIG. 5 shows an alternative embodiment of the device in which the firstcatheter 18 and second catheter 20 of the treatment assembly 16 may beinserted alongside an endoscope 12 which may be used to provide forvisualization. Due to the small size of the catheters, this embodimentis feasible.

FIGS. 6A to 6C illustrate an example for a placement procedure for theassembly for the treatment of a body lumen such as the esophagus ES. Thecatheters may be inserted simultaneously or separately through theworking channel of the endoscope 12. In one example, the larger firstcatheter 18 may be inserted first followed by insertion of the secondcatheter 20 within the lumen of the first catheter 18. Once both singleor multi-lumen balloon catheters have been inserted and after theendoscope 12 has been advanced through the esophagus ES and intoproximity to the tissue treatment region, the distal balloon 24 may beadvanced to define the distal end of the treatment area and inflated(e.g., with chilled, room or body temperature fluid) while undervisualization through the endoscope 12, as shown in FIG. 6A. Theendoscope 12 may then be pulled back until the proximal end of thedesired treatment area has been identified and the proximal balloon 22may be slid over the shaft of the second catheter 20 and inflated (e.g.,with chilled, room or body temperature fluid) at a site just proximal tothe most proximal portion of the lesion, as shown in FIG. 6B.

With the treatment area 40 now enclosed by these balloons, an optionalpressure capsule 42 (e.g., solid state, piezoeletric or other pressuresensing method) may be inflated and the treatment may proceed, as shownin FIG. 6C. The treatment session then exposes the lumen or body cavityto fluid pressurized to a positive pressure in the range of, e.g., 5-100cmH2O (although this pressure may be maintained at a level below aninflation pressure of the inflation balloons) at temperatures between,e.g., 50 and 100 degrees Celsius, for a period of, e.g., 1 second to 10minutes. Additionally and/or alternatively, the treatment area 40 may belavaged for a period of time with an anesthetic (e.g., lidocaine orbupivicaine) to reduce pain with the procedure prior to the applicationof thermal energy or other active compounds. Accordingly, ablation maybe accomplished at a consistent depth of, e.g., about 0.5 mm, throughoutthe esophagus ES.

FIGS. 7A to 7C illustrate another example for treatment of an enclosedbody cavity (shown here as a bladder BL). In this example, a singleballoon may be used to effect infusion and extraction of the treatmentfluid. Pressure may be monitored to ensure that the therapy is safe anda relatively lower temperature fluid may be used (e.g., 42-100 C.) sothat the entire cavity may see a controlled, uniform thermal load. Theorder or catheter placement may vary as may the sequence for ballooninflation or exposure to active or inactive liquid or vapors in this orany embodiment of the device. As shown in FIG. 7A, an endoscope (orcystoscope) 12 may be inserted into the target organ BL then fluidcatheter 20 may be advanced into the lumen. With the endoscope 12inserted and occlusion balloon inflated 24 (e.g., with unheated fluid)to seal the organ, a pressure sensor 42 may also be optionally inflatedto measure pressure, as shown in FIG. 7B. Optionally, an anesthetic orpre-treatment medication may be delivered into the bladder BL, if sodesired. Then, a high or low temperature fluid 80 may be circulatedwithin the bladder BL under pressure adequate to safely distend theorgan to ensure complete treatment, as shown in FIG. 7C.

FIGS. 8A to 8C illustrate another example for treatment where the use afluid lavage to prepare the treatment area (here shown as the bladderBL) may be accomplished prior to application of thermal (or cooling)energy and/or active compounds. As previously described, the endoscope12 and catheter 20 may be introduced into the bladder BL andsubsequently sealed with the occlusion balloon 24, as shown in FIGS. 8Aand 8B. Preparation of the treatment area may involve use of ananesthetic to decrease pain during therapy or the use of an arterialconstrictor to reduce blood flow to the organ or lumen. Alternatively,other pre-treatment fluids 82 may include, e.g., anesthetic, vascularconstrictor, chilled fluid, active component antidote, etc. Thepre-treatment fluid 82 may be evacuated (or left within the bladder BL)and the lavage with the treatment fluid 80 may be introduced into thebladder BL for treatment, as shown in FIG. 8C.

Alternatively, the pre-treatment fluid 82 may also be chilled (orheated) to cool (or warm) the lumen or organ prior to treatment so thatthe thermal (or cooling) energy may be applied to the internal surfaceof the lumen or body cavity with minimal transmission or conduction ofthe elevated (or cooling) temperatures to the submucosal tissues (ortissues lining the body organ or lumen). Utilizing the pre-treatment ofthe area may avoid damage to the underlying tissues to thereby avoidmany of the complications of therapy. For example, strictures and/orstenosis (or tightening) of the tissue can be avoided by controlling thedepth of penetration which may be controlled by pre-treating the areawith a chilled fluid so that the submucosa can absorb significantamounts of heat without reaching damaging temperatures.

The depth of penetration may also be controlled through the use of alower temperature fluid for thermal ablation so that the submucosa cancool itself with its robust vascular circulation (which is less robustin the mucosa and epithelium). In the event that an active compound isused, as well, an antidote to this compound may be delivered to thepatient (either systemically or as a local pre-treatment) so that theunderlying tissues and submucosa are not damaged. One example of this isthe use of powerful antioxidants (systemically or locally) prior tolavage of the esophagus with, e.g., methotrexate. The methotrexate mayhave a powerful effect on the tissues to which it is directly exposed inthe lumen or body cavity, but the anti-oxidants may prevent deeperpenetration of the methotrexate. The neutralizing compound may also beplaced within the balloon or in the lumen of surrounding lumens or bodycavities to prevent exposure of these areas in the event of balloonrupture.

FIG. 9 shows another example where the distal occlusion member may beconfigured into an umbrella-like element 90 which may be expanded in thestomach ST and placed over a tissue region which is typically difficultto occlude by a balloon. For instance, such a shape may allow forablation of the lower esophageal sphincter LES at the gastroesophagealjunction (or other sphincter region if used elsewhere). The expandable,umbrella-like structure 90 may form a firm seal at this site whileallowing the ablation fluid (hot or cold) to contact the entiregastroesophageal junction. Once expanded, the umbrella-like element 90maybe held firmly against the stomach ST by traction on the endoscope 12or by a tensioning element on the catheter and balloon itself.

In addition, this element 90 may optionally incorporate a biased orspring-loaded element or other external force mechanism to providesteady pressure and a firm seal against the stomach lining. Alternativestructures may also incorporate a more complex, nitinol cage (or otherrigid material) connected by a thin, water-tight film. For example,nitinol may be used to decrease the overall profile of the obstructionelement and increase its strength and durability.

FIG. 10 shows another example which utilizes an endoscopic balloonsheath utilized as a distal occluder allowing for exposure and treatmentof the distal gastroesophageal junction. In this embodiment, the secondcatheter 20 may have a distal occlusion balloon 100 which may be passedthrough the working channel of the endoscope 12 or through a channelincorporated into the balloon sheath itself (outside of the actualendoscope). Once expanded into an enlarged shape, the balloon 100 may beretracted to fit entirely over the lower esophageal junction LES to formthe distal seal by traction on the endoscope 12 or by a tensioningelement on the catheter and balloon itself. This gastric occlusionballoon may allow for exposure of the gastroesophageal junction whilepreventing fluid flow into the stomach ST. The balloon 22 may beconfigured to be saddle-shaped, circular, wedge-shaped, etc. It may alsobe self-expanding and non-inflatable.

Additionally, the proximal balloon 22 may be configured to be part ofsheath that is placed over the tip of the endoscope 12 or it may beformed directly upon the endoscope tip itself. An inflation lumen mayrun inside the endoscope 12 or it may run alongside the endoscope 12 ina sheath or catheter. The balloon sheath may also incorporate atemperature sensor, pressure sensor, etc. Moreover, the proximalocclusion balloon 22 may optionally incorporate a temperature orpressure sensing element for the therapy and it may be positioned eitherthrough the working channel(s) of the endoscope 12 or alongside theendoscope 12 within the endoscopic balloon sheath.

In yet another embodiment, in order to reduce the risks associated withfluid flow and lavage, a fluid or gel may be infused into the esophagusbetween the balloons then heated or frozen in situ in order to providethe desired ablative effect without circulating any fluid or gel. In oneexample of this configuration, a gel may be infused into the esophagusand pressurized to a safe level (e.g., 30-100 mmHg) which may be thenrapidly chilled using, for example, a compressed gas and/or a Peltierjunction-type cooling element. The gel may freeze at a temperature belowthat of water and allow for rapid transmission of the ablativetemperature to the tissues being treated. This gel may also be a liquidwith a freezing point below that of water in which case the treatmentzone may be lavaged with this fluid prior to treatment to remove freewater and prevent crystal formation during therapy. Once the therapy hasbeen completed, the gel or liquid may be removed or left in theesophagus to be passed into the stomach. In the event that a Peltiercooling or heating element is used, the polarity may be reversed oncetherapy is complete in order to reverse the temperature and terminatethe ablation session.

The distance from the lower end of the distal most portion of thecatheter can be on the order of about 150 mm. The distance between theproximal and distal balloons are adjustable by the operator but can beadjusted, e.g., from as small as 0 mm to as large as 25 cm. Thetreatment zone may have a range of, e.g., 3 to 15 cm.

In yet an additional embodiment, an energy generator (e.g., a RFelectrode or hot wire or other energy source) may be advanced into thetreatment area in a protective sheath (to prevent direct contact withbody tissues) and energy may be applied to the treatment fluid to heatit to the desired temperature. Once the fluid is adequately heated andenough time has passed to achieve a controlled ablation, the fluid maythen be evacuated or neutralized with the influx of colder fluid. Thisembodiment would allow for a very low-profile design and would notrequire any fluid heating element outside of the body.

In another variation, the cavity or lumen may be exposed to the hotwater at a temperature of less than, e.g., 100 degrees Celsius, butgreater than, e.g., 42 degrees Celsius, to allow for easier control ofthe treatment due a longer treatment period. Ranges for optimalhyperthermic treatment include temperatures between, e.g., 42 and 100 C.and exposure periods ranging from, e.g., 15 seconds to 15 minutes. Inthis embodiment, treatment may be effected with an active (e.g.,Methotrexate) or inactive fluid at a temperature of, e.g., 90 degreesC., for a period of, e.g., 5-60 seconds, depending on the depth ofpenetration desired.

FIG. 11 shows another example of an endoscopic balloon sheath which maybe used to provide proximal occlusion of the treatment area 40 and mayhouse one or more of the temperature and pressure sensors. Thisvariation may incorporate a stirring/agitating or recirculationmechanism 110 incorporated into the device which may actuated within thetreatment area 40 once the treatment fluid has been introduced to allowfor even cooling/heating. The distal occlusion balloon 100 may beinflated within the stomach ST and pulled proximally with controlledtraction against the gastric portion of the lower esophageal sphincterLES, as previously described.

In this example, a chilled liquid lavage (or vapor infusion) may then beinitiated and the tissue ablated via freezing. A pre-treatment lavage,e.g., a hypertonic, hyperosmotic saline solution, may be introduced withabove freezing temperatures followed by a sub-zero temperature lavage toablate the tissues within the treatment area 40. The hypertonic,hyperosmotic fluid may achieve temperatures down to, e.g., −40 degreesC., without creating ice crystals in the treatment area 40 due to thepre-treatment lavage removing any free water. The treatment fluidfollowing the pre-treatment lavage may have temperatures of, e.g., −2degrees C. to −40 degrees C., for ablation or more particularly atemperature range of, e.g., −5 degrees C. to −20 degrees C. Thistemperature range may allow for freezing and crystal formation in theexposed tissues without damaging the underlying submucosa (which isprotected by the circulation of body temperature blood that preventsfreezing). This temperature range can also be easily achieved withhypersalination of aqueous fluid using sodium chloride and may inhibitany undesired damage to tissues with brief contact. Also, the use of aheavily salinated or other sub-zero solution lavage may provide optimalsealing of the occluding balloons in that any sub-zero temperaturesoutside of the pre-lavaged treatment zone may form an impaction of icecrystals and prevent any further fluid flow outside of the treatmentzone. This hypersalinated water solution is but one freezing solution,though, and any aqueous or non-aqueous liquid or vapor that can beinfused and extracted at this temperature could be used. Alternatively,cryoablative fluid can simply comprise nitrous oxide (N₂O) or be formedby cooling ethanol or another aqueous or lipophilic fluid with subzerocooling temps with compressed gas or dry ice. In another alternative,compressed CO₂ or dry ice may be introduced into the fluid (e.g.,ethanol, butylenes glycol, propylene glycol, etc) to cool it to, e.g.,−50 degrees C. or below.

Despite the potential for toxicity, ethanol may be used for a liquidlavage since ethanol resists freezing down to −118 C. and is relativelybiocompatible although ethanol is dose dependent for toxicity. A liquidlavage with about 75% to 99.9% ethanol concentrations may be utilized togood effect and have been demonstrated to show that a freeze layerdevelops very rapidly which also inhibits further ethanol absorption.For instance, a concentration of 95% ethanol may be introduced at atemperature of about, e.g., −80 to −50 degrees C., for a treatment timeof about, e.g., 5 minutes, utilizing 0.25 to 0.5 liters of the cryogenicfluid. An ethanol copper composition may also be very useful sinceethanol resists freezing whereas aqueous fluids will freeze and expandthereby moving the metal particle out of direct contact with the tissue.

In the event that nitrous oxide is used as the cryogenic fluid, thenitrous may be introduced through a nozzle or spray at a pressure of,e.g., 600-800 psi, at a temperature of about −88 degrees C. Such atemperature and pressure may be utilized for a treatment time of about,e.g., 3 minutes.

The use of a subzero solution within this range may also allow for finecontrol of the treatment depth as tissue damage would not begin to occuruntil a temperature differential of about 37 degrees C. is achieved(assuming a body temperature of 37° C.), but once this threshold isreached tissue damage occurs rapidly due to ice crystal formation. Incontrast, tissue damage is on a continuous spectrum with hyperthermiaand damage may begin to occur at a temperature differential of, e.g., 5degrees C. Thus, the ability of the vasculature to protect theunderlying tissues from damage is greatly reduced due to the smalldifference between the temperature of protective blood versus thetemperature of the ablating fluid. With hypothermic lavage, theprotective blood may differ by, e.g., 37 degrees C., in temperature andmay thus allow for control of ablation depth based on the temperature ofthe fluid lavage and the time of exposure.

FIG. 12 illustrates another variation where a conforming balloon 111having an adjustable size in diameter as well as in length may bepositioned along or near the distal end of the catheter 18. Theconforming balloon 111 may be advanced within the esophagus (shown herein the esophagus but applicable to any cavity) in a collapsed state.Once the balloon 111 has been desirably positioned along the length ofthe esophagus ES to be treated, the catheter 18 may optionally utilize avacuum which may be drawn along the entire length of the balloon 111through perforations or openings in the balloon 111 to serve as asafeguard to prevent migration of ablation liquid, gas, and/orconductive material in the event of balloon rupture. The vacuum may alsobe utilized to remove air, fluids or particulate between the outer wallof the balloon 111 and the tissue to improve contact and thermaltransfer from the hyperthemic or cryogenic fluid and to the tissue.Additionally and/or alternatively, a distal vacuum may be drawn througha distal port 117 distal to the balloon 111 either alone or inconjunction with a proximal vacuum port 115 proximal to the balloon 115.

With the catheter 18 and balloon 111 desirably positioned for treatment,an insulating sheath 113 may be advanced over the catheter 18 and overthe length of the balloon 111 to vary an inflation length of the balloon111 emerging from the insulating sheath 113. The variable length of theinflated balloon 111 may be adjusted to allow for treatment of anyvarying lengths of the esophagus ES during a single ablation treatment.Such a design may prevent dangerous ablation overlap zones of ablatedtissue.

The balloon 111 itself may be comprised of a compliant or non-compliantmaterial but in either case be capable of directly contacting thetissues to be ablated. The balloon 111 may accordingly be filled with ahyperthemic or cryogenic material and/or may use liquid, gas, and/orconductive solids, as described herein.

Although illustrated esophageal therapy, this therapy could be used inany body cavity/lumen for therapeutic purposes including, but notlimited to, gastrointestinal therapy, stomal tightening (e.g., postbariatric surgery), urogynecologic uses (treatment of cervicalpre-cancers or cancers, endometrial lining treatment, stressincontinence therapy), prostate therapy, intravascular therapy (e.g.,varicose veins) or treatment of any other body cavity/lumen. In theevent that an entire body cavity is being treated (e.g., the entireuterus) a single balloon system may suffice to exclude the entirecavity. The fluid cycling or dwell may then be accomplished with use ofa pressure-controlled exposure of the cavity or lumen.

FIGS. 13A and 13B show another example of how the system may beintroduced into, e.g., a uterus UT, through the cervix for treatment viathe lavage catheter 20. In this example, the catheter 20 may have adiameter of about, e.g., 8 mm, or in other examples, a diameter ofabout, e.g., less than 6 mm. Infusion of the lavage fluid may fullydistend or partially distend the uterine walls. Optionally, catheter 20may incorporate a tip 120 to perform one or more functions including,e.g., an expandable cage or scaffold to prevent direct exposure of acryoprobe to the tissue walls of the uterus UT, an agitator orrecirculator to ensure even distribution of cryoablation effect, etc. Aspreviously described, the system may be used with lavage or withinfusion then cryoprobe chilling of fluid. In an alternate embodiment,infusion of an antifreeze fluid and insertion of the cryprobe may bedone separately with chilling of the anti-freeze done after thecryoprobe insertion.

In this and other examples, the therapy may be guided bytime/temperature tracking or visualization (e.g., hysteroscope,endoscope, ultrasound, etc.). Pressure may be regulated by a pressuresensor in line with the infusion or extraction lumen or a dedicatedpressure lumen in a multi-lumen catheter. Additionally, pressure mayalso be regulated by limiting infusion pressure (e.g., height ofinfusion bag, maximum pressure of infusion pump, etc.). Any organ, bodycavity or lumen may be treated using the described lavage and/orinfusion/cryoprobe technique described here for the uterus.

FIGS. 14A and 14B illustrate another variation of a treatment systemwhich utilizes a thermally conductive array of fibers, cage, or lattice130 which may be deployed within the uterus UT. In this variation, theendoscope 12 may be advanced through the cervix and at least partiallyinto the uterus UT where the array of fibers or lattice 130 may bedeployed from the endoscope 12 distal end where the array 130 may bepositioned in a compressed state for delivery, as shown in FIG. 14A. Thearray 130 may be advanced into the uterus UT where it may then beexpanded into a deployed configuration 130′, as shown in FIG. 14B. Theindividual cryogenic probes of the expanded array 130′ may be in fannedout relative to the distal end of the endoscope 12 in various directionsto come into direct contact or close proximity to the tissue to betreated.

Following deployment, the deployed array 130′ may be cooled rapidly totransmit the heat within the uterine walls to the array 130′ to providea consistent cryoablative effect throughout the body cavity or lumen.The members of the array 130′ may be cooled either via conductivecooling or by an infusion of a cooling fluid (as described herein)through the members of the array 130′. Similar to the conductive fluid,the cooled array 130′ may provide for the consistent ablation of theentire lumen with a single application of the array 130′. The individualmembers of the array 130′

Additionally and/or alternatively, the array 130′ may be used inconjunction with a fluid infusion and/or lavage in order to optimizetherapy. One or more sizes and shapes of the array 130′ may be availabledepending on the size and shape of the cavity to be treated. Moreover,the array 130′ may be formed from any material so long as it has athermal conductivity greater than, e.g., 2 W/m-K, such as a metal with arelatively high thermal conductivity.

FIG. 15 shows another variation of a device which may utilize cryogeniclavage treatment within the uterus UT. In this example, the distal endof the endoscope 12 may be advanced through the cervix CV and into theuterus UT where a cryoprobe 140 may be deployed, as shown. One or moreinflatable balloons 144 may be expanded, e.g., within the external os,or a balloon 142 along the outer surface of the endoscope 12 may beinflated within the length of the os itself. Alternatively, a singleballoon (e.g., having an hourglass or dumbbell shape) may be inflated toblock both the external os and the length of the os itself. With theuterus UT obstructed, the cryogenic treatment or lavage may be performedwithin the uterine lumen.

Another variation is illustrated in FIG. 16 which shows endoscope 12advanced through the cervix CV with the distal end 156 positioned withinthe uterine lumen. An optional balloon 152 located near the endoscopedistal end may be inflated within the uterus UT and then pulledproximally against the internal os with a fixed amount of tension toobstruct the opening. Additionally and/or alternatively, a proximalballoon 154 positioned along the endoscope 12 proximally of where thecervix CV is located may also inflated to further provide forobstruction of the entire os. Then external cervical engagement portion,e.g., proximal balloon 154, may be fixed in place relative portion ofthe endoscope 12 spanning the cervical os to provide consistent tension.The proximal balloon 154 may also have a spring-type function to providefor consistent tension regardless of tissue relaxation andaccommodation.

With the uterus UT obstructed, the endoscope 12 may then be used toprovide for the cryogenic treatment or lavage. Optionally, the endoscope12 may also incorporate one or more vacuum ports along the length of theshaft to seal and provide a safeguard against fluid flow out of theuterus UT.

Optionally, the uterine cornu may be temporarily obstructed to block theopenings of one or both Fallopian tubes prior to the cryogenictreatment. The occlusive element(s) 158A, 158B may comprise, e.g.,balloons, inserts, energy-based ablation to contract the aperture,hydrophilic or hydrophobic gel-based solutions, or any other modalitythat is capable of reversibly or irreversibly sealing the Fallopiantube. The optional Fallopian tube occlusion may be temporary orpermanent (if sterility is desired).

Once the cryogenic procedure has been completed, the occlusive elements158A, 158B may be removed or allowed to passively erode. Alternatively,they may be left occluded for those desiring sterility. Occluding theuterine cornu prior to a lavage may allow for greater fluid pressure andfluid flow within the uterus UT.

FIGS. 17A and 17B illustrate another variation of a low-pressureconforming balloon. In this variation, a conforming balloon 160 may bedeployed from the distal end 156 of the endoscope 12 and then inflatedwith the cryogenic liquid/gas (as described herein) while in uterus UT.The balloon 160 may be formed to resist rupture at low and hightemperatures and may be further configured to conform well to theanatomy of the uterus UT. For example, the balloon 160 when inflated mayhave a shape which approximates the lumen in which it is inflated and/orcome in various sizes to accommodate different patient anatomies. In thepresent example, the expanded balloon 160′ may be formed to taper andhave two portions rounded portions for expanding into intimate contactat the uterine cornu UC, as shown, without painful deformation ordistention of the uterus UT at a pressure, e.g., less than 150 mmHg.

Moreover, the expanded balloon 160′ may have a wall which is relativelythin (e.g., 0.040 in. or less) to facilitate thermal conduction throughthe balloon. The balloon 160 may also be sufficiently thin such thatfolding of the balloon 160 on itself does not create a significantthermal barrier allowing for an even ablation in the event that anon-compliant balloon is used. For treatment, the expanded balloon 160′may be filled with the cryogenic liquid, gas or a thermally conductivecompound (as described above) to subject the contacted tissue to eithercryogenic and/or hyperthermic injury (e.g., steam, plasma, microwave,RF, hot water, etc). Additionally and/or alternatively, the balloon 160′may also be used to transmit photodynamic therapy light to the uterus UTor esophagus ES. This modality may be used to achieve ablation of anybody cavity or lumen.

Additionally, one or more vacuum ports may be used anywhere along thelength of the shaft to seal and provide a safeguard against fluid flowout of the uterus UT in the event of balloon rupture. Additionally, oneor more inflatable os balloon 160 may also be used to block the internalor external os, as also described above.

In another variation, to facilitate the balloon expanding and conformingreadily against the tissue walls of the uterus UT, the balloon may beinflated with a gas or liquid. Alternatively, as shown in FIGS. 18A to18D, the balloon may be filled partially or completely with a conductivematerial. As shown in FIG. 18A, once the elongate shaft 170 has beenintroduced through the cervix CV and into the uterus UT, the distalopening 172 of the shaft 170 may be positioned distal to the internal osand balloon 174 may be deployed either from within the shaft 170 or froman external sheath (described below in further detail). The balloon maybe deployed and allowed to unfurl or unwrap within the uterus UT, asshown in FIG. 18B. The cooling probe 178 may be introduced through theshaft 172 and into the balloon interior (or introduced after insertionof the conductive elements).

Because the balloon 174 is used to contact the tissue and thermallyconduct the heat through the balloon, the balloon material may becomprised of various materials such as polyurethane, fluorinatedethylene propylene (FEP), polyether ether ketone (PEEK), low densitypolyethylene, polyethylene terephthalate (PET), polyvinylidene fluoride(PVDF), or any number of other conformable polymers. Moreover, theballoon material may have a thickness which remains flexible and strongyet sufficiently thermally conductive, e.g., about 0.0005 to 0.015 in.Such a thickness may allow for the balloon to remain supple enough toconform desirably to the underlying tissue anatomy and may also providesufficient clarity for visualizing through the material with, e.g., ahysteroscope.

The conductive elements 182 may be introduced into the balloon interiorthrough an annular opening 180 within the distal end 172 of the shaft,as shown in FIG. 18C, until the balloon 174 is at least partially orcompletely filled with the elements 182. The conductive elements 182 maygenerally comprise any number of thermally conductive elements such ascopper spheres or some other inert metal such as gold. These conductiveelements 182 may be atraumatic in shape and are small enough to fill theballoon interior and conform the balloon walls against the uterine wallsUW to ensure consistent contact with the tissue, e.g., about 20 ml involume of the elements 182. The conductive elements 182 may also help tofill any air pockets which may form particularly near the taperedportions 176 of the balloon and insulate the tissue from the ablativeeffects of the cryoablative fluid. For instance, the conductive elements182 may be formed into spheres having a diameter of, e.g., 0.8 mm to 4mm or larger. To ensure that conductive elements 182 are fully andevenly dispersed throughout the balloon interior, the elements 182 maybe introduced through the shaft 170 via an ejector or push rod, auger,compressed air, etc. In particular, the conductive elements 182 may fillthe tapered portions 176 of the balloon 174 to ensure that the balloonis positioned proximate to and in contact with the uterine cornu UC tofully treat the interior of the uterus UT, as shown in FIG. 18D.

With the conductive elements 182 placed within the balloon 174, thecryoablative fluid may be introduced within and through the balloon 174such that the conductive elements 182 facilitate the thermal transferfrom the contacted uterine walls UW. Once the cryoablative treatment hasbeen completed, the conductive elements 182 may be removed through theshaft 170 via a vacuum force or other mechanical or electromechanicalmechanisms and the balloon 174, once emptied, may also be withdrawn fromthe uterus UT.

The cooling probe 178 introduced into the interior of the balloon 174may comprise a number of different configurations which facilitate theintroduction of the cryoablative fluid into the balloon 174. One suchvariation, similar to the variation shown above in FIG. 14B, isillustrated in the detail view of FIG. 19. In this variation, the shaft178 may have one or more cooling members 190A, 190B, 190C, 190D whichproject from the distal end of the shaft 178 at various angles. Althoughillustrated with four cooling members extending from the shaft 178, anynumber of cooling members may be used at a variety of different anglesand lengths as desired. Moreover, the cooling members may be fabricatedfrom a number of materials, e.g., polyimide, Nitinol, etc., which aresufficiently strong and temperature resistant for the relatively lowtemperature of the fluid. Each of the cooling members 190A, 190B, 190C,190D in this example may each have an occluded tip 192 and at least oneopening 194 defined along the side of the cooling member. Thecryoablative fluid may be flowed through the shaft 178 and into eachcooling member where the fluid may then be sprayed or ejected throughthe respective openings 194 for distribution throughout the interior ofthe balloon for cooling the contacted uterine tissue.

Another variation of the cooling probe is illustrated in the detail viewof FIG. 20 which shows elongate shaft 178 having a rotating base 200 andspray member 202 positioned upon shaft 178. The spray member 202 mayhave a surface which is meshed, latticed, perforated, etc. such that thecryoablative fluid introduced through the shaft 178 may enter therotating base 200 and spray member 202 where it may be evenly dispersedthrough the spray member 202 and into the interior of the balloon 174for treatment. The pressure of the fluid may rotate the base 200 aboutits longitudinal axis, as shown, to further facilitate the distributionof the cryoablative fluid within the balloon 174.

The cooling probe 178 as well as the balloon assembly may be variouslyconfigured, for instance, in an integrated treatment assembly 210 asshown in the side view of FIG. 21A. In this variation, the assembly 210may integrated the elongate shaft 170 having the balloon 174 extendingtherefrom with the cooling probe 178 positioned translatably within theshaft 170 and balloon 174. A separate translatable sheath 212 may bepositioned over the elongate shaft 170 and both the elongate shaft 170and sheath 212 may be attached to a handle assembly 214. The handleassembly 214 may further comprise an actuator 216 for controlling atranslation of the sheath 212 for balloon 174 delivery and deployment.The sheath 212 may be configured to have a diameter of, e.g., 5.5 mm orless, to prevent the need for dilating the cervix.

With the sheath 212 positioned over the elongate shaft 170 and balloon174, the assembly 210 may be advanced through the cervix and into theuterus UT where the sheath 212 may be retracted via the handle assembly214 to deploy the balloon 174, as shown in FIG. 21B. As described above,once the balloon 174 is initially deployed from the sheath 212, it maybe expanded by an initial burst of a gas, e.g., air, carbon dioxide,etc., or by the cryogenic fluid. In particular, the tapered portions ofthe balloon 174 may be expanded to ensure contact with the uterinecornu. The handle assembly 214 may also be used to actuate and control alongitudinal position of the cooling probe 178 relative to the elongateshaft 170 and balloon 174 as indicated by the arrows.

In another variation of the treatment assembly, FIG. 21C shows aperspective view of a cryoablation assembly having a handle assembly 211which may integrate the electronics and pump assembly 215 within thehandle itself. An exhaust tube 213 may also be seen attached to thehandle assembly 211 for evacuating exhausted or excess cryoablativefluid or gas from the liner 174. Any of the cryogenic fluids or gasesdescribed herein may be utilized, e.g., compressed liquid-to-gas phasechange of a compressed gas such as nitrous oxide (N₂O), carbon dioxide(CO₂), Argon, etc. The cooling probe 178 may be seen extending fromsheath 212 while surrounded or enclosed by the balloon or liner 174.Hence, the handle assembly 211 with coupled cooling probe 178 and liner174 may provide for a single device which may provide for pre-treatmentpuff-up or inflation of the liner 174, active cryoablation treatment,and/or post-treatment thaw cycles.

The handle assembly 211 may also optionally incorporate a display forproviding any number of indicators and/or alerts to the user. Forinstance, an LCD display may be provided on the handle assembly 211 (orto a separate control unit connected to the handle assembly 211) wherethe display counts down the treatment time in seconds as the ablation isoccurring. The display may also be used to provide measured pressure ortemperature readings as well as any number of other indicators, symbols,or text, etc., for alerts, instructions, or other indications. Moreover,the display may be configured to have multiple color-coded outputs,e.g., green, yellow, and red. When the assembly is working through theideal use case, the LED may be displayed as a solid green color. Whenthe device requires user input (e.g. when paused and needing the user topress the button to re-start treatment) the LED may flash or displayyellow. Additionally, when the device has faulted and treatment isstopped, the LED may flash or display a solid red color.

FIG. 21D shows the handle assembly 211 in a perspective exploded view toillustrate some of the components which may be integrated within thehandle 211. As shown, the liner 174 and sheath 212 may be coupled to asheath bearing assembly 219 and slider base block assembly 221 forcontrolling the amount of exposed treatment length along the coolingprobe 178 (and as described in further detail below). An actuatablesheath control 223 may be attached to the slider base block assembly 221for manually controlling the treatment length of the cooling probe 178as well. Along with the electronics and pump assembly 215 (which mayoptionally incorporate a programmable processor or controller inelectrical communication with any of the mechanisms within the handle211), an exhaust valve 217 (e.g., actuated via a solenoid) may becoupled to the exhaust line 213 for controlling not only the outflow ofthe exhausted cryoablation fluid or gas but also for creating orincreasing a backpressure during treatment, as described in furtherdetail below.

In one example of how the handle assembly 211 may provide for treatment,FIGS. 21E to 21G illustrate schematic side views of how the componentsmay be integrated and utilized with one another. As described herein,once the sheath 212 and/or liner 174 has been advanced and initiallyintroduced into the uterus, the liner 174 may be expanded or inflated ina pre-treatment puff up to expand the liner 174 into contact against theuterine tissue surfaces in preparation for a cryoablation treatment. Asillustrated in the side view of FIG. 21E, a pump 225 integrated withinthe handle assembly 211 may be actuated and a valve 229 (e.g.,actuatable or passive) fluidly coupled to the pump 225 may be opened (asindicated schematically by an “O” over both the pump 225 and valve 229)such that ambient air may be drawn in through, e.g., an air filter 227integrated along the handle 211, and passed through an air line 231within the handle and to an exhaust block 233. The exhaust block 233 andair line 231 may be fluidly coupled to the tubular exhaust channel whichextends from the handle 211 which is further attached to the coolingprobe 178. As the air is introduced into the interior of the liner 174(indicated by the arrows), the liner 174 may be expanded into contactagainst the surrounding uterine tissue surface.

A cryogenic fluid line 235 also extending into and integrated within thehandle assembly 211 may be fluidly coupled to an actuatable valve 237,e.g., actuated via a solenoid, which may be manually closed orautomatically closed (as indicated schematically by an “X” over thevalve 237) by a controller to prevent the introduction of thecryoablative fluid or gas into the liner 174 during the pre-treatmentliner expansion. An infusion line 239 may be fluidly coupled to thevalve 237 and may also be coupled along the length of the sheath 212 andprobe 178, as described in further detail below. The exhaust valve 217coupled to the exhaust line 213 may also be closed (as indicatedschematically by an “X” over the valve 217) manually or automatically bythe controller to prevent the escape of the air from the exhaust block233.

During this initial liner expansion, the liner 174 may be expanded in agradual and controlled manner to minimize any pain which may beexperienced by the patient in opening the uterine cavity. Hence, theliner 174 may be expanded gradually by metering in small amounts of air.Optionally, the pump 225 may be programmed and controlled by a processoror microcontroller to expand the liner 174 according to an algorithm(e.g., e.g. ramp-up pressure quickly to 10 mm Hg and then slow-down theramp-up as the pressure increases to 85 mm Hg) which may be stopped orpaused by the user. Moreover, the liner 174 may be expanded to a volumewhich is just sufficient to take up space within the uterine cavity.After the initial increase in pressure, the pressure within the liner174 may be optionally increased in bursts or pulses. Moreover,visualization (e.g., via a hysteroscope or abdominal ultrasound) may beoptionally used during the controlled gradual expansion to determinewhen the uterine cavity is fully open and requires no furtherpressurization. In yet another variation, the liner 174 may becyclically inflated and deflated to fully expand the liner. Theinflations and deflations may be partial or full depending upon thedesired expansion.

In yet another alternative variation, the system could also use anamount of air pumped into the liner 174 as a mechanism for detectingwhether the device is in a false passage of the body rather than theuterine cavity to be treated. The system could use the amount of timethat the pump 225 is on to track how much air has been pushed into theliner 174. If the pump 225 fails to reach certain pressure levels withina predetermined period of time, then the controller may indicate thatthe device is positioned within a false passage. There could also be alimit to the amount of air allowed to be pushed into the liner 174 as away to detect whether the probe 178 has been pushed, e.g., out into theperitoneal cavity. If too much air is pushed into the liner 174 (e.g.,the volume of air tracked by the controller exceeds a predeterminedlevel) before reaching certain pressures, then the controller mayindicate the presence of a leak or that the liner 174 is not fullyconstrained by the uterine cavity. The liner 174 may also incorporate arelease feature which is configured to rupture if the liner 174 is notconstrained such that if the system attempts to pump up the liner 174 totreatment pressure (e.g., 85 mmHg), the release feature will rupturebefore reaching that pressure.

Once the liner 174 has been expanded sufficiently into contact againstthe uterine tissue surface, the cryoablation treatment may be initiated.As shown in the side view of FIG. 21F, the air pump 225 may be turnedoff and the valve 229 may be closed (as indicated schematically by an“X” over the pump 225 and valve 229) to prevent any further infusion ofair into the liner 174. With the cryogenic fluid or gas pressurizedwithin the line 235, valve 237 may be opened (as indicated schematicallyby an “O” over the valve 237) to allow for the flow of the cryogenicfluid or gas to flow through the infusion line 239 coupled to the valve237. Infusion line 239 may be routed through or along the sheath 212 andalong the probe 178 where it may introduce the cryogenic fluid or gaswithin the interior of liner 174 for infusion against the liner 174contacted against the surrounding tissue surface.

During treatment or afterwards, the exhaust valve 217 may also be opened(as indicated schematically by an “O” over the valve 217) to allow forthe discharged fluid or gas to exit or be drawn from the liner interiorand proximally through the cooling probe 178, such as through the distaltip opening. The fluid or gas may exit from the liner 174 due to apressure differential between the liner interior and the exhaust exitand/or the fluid or gas may be actively drawn out from the linerinterior, as described in further detail herein. The spent fluid or gasmay then be withdrawn proximally through the probe 178 and through thelumen surrounded by the sheath 212, exhaust block 233, and the exhausttube 213 where the spent fluid or gas may be vented. With the treatmentfluid or gas thus introduced through infusion line 239 within the liner174 and then withdrawn, the cryogenic treatment may be applieduninterrupted.

Once a treatment has been completed, the tissue of the uterine cavitymay be permitted to thaw. During this process, the cryogenic fluiddelivery is halted through the infusion line 239 by closing the valve237 (as indicated schematically by an “X” over the valve 237) whilecontinuing to exhaust for any remaining cryogenic fluid or gas remainingwithin the liner 174 through probe 178, through the lumen surrounded bysheath 212, and exhaust line 213, as shown in FIG. 21G. Optionally, thepump 225 and valve 229 may be cycled on and off and the exhaust valve217 may also be cycled on and off to push ambient air into the liner 174to facilitate the thawing of the liner 174 to the uterine cavity.Optionally, warmed air or fluid (e.g., saline) may also be pumped intothe liner 174 to further facilitate thawing of the tissue region.

As the spent cryogenic fluid or gas is removed from the liner 174, adrip prevention system may be optionally incorporated into the handle.For instance, a passive system incorporating a vented trap may beintegrated into the handle which allows exhaust gas to escape butcaptures any vented liquid. The exhaust line 213 may be elongated toallow for any vented liquid to evaporate or the exhaust line 213 may beconvoluted to increase the surface area of the exhaust gas tube topromote evaporation.

Alternatively, an active system may be integrated into the handle orcoupled to the handle 211 where a heat sink may be connected to atemperature sensor and electrical circuit which is controlled by aprocessor or microcontroller. The heat sink may promote heat transferand causes any liquid exhaust to evaporate. When the temperature of theheat sink reaches the boiling temperature of, e.g., nitrous oxide(around −89° C.), the handle may be configured to slow or stop thedelivery of the cryogenic fluid or gas to the uterine cavity.

The pre-treatment infusion of air as well as the methods for treatmentand thawing may be utilized with any of the liner, probe, or apparatusvariations described herein. Moreover, the pre-treatment, treatment, orpost-treatment procedures may be utilized altogether in a singleprocedure or different aspects of such procedures may be used in varyingcombinations depending upon the desired results.

Additionally and/or optionally, the handle 211 may incorporate anorientation sensor to facilitate maintaining the handle 211 in adesirable orientation for treatment. One variation may incorporate aball having a specific weight covering the exhaust line 213 such thatwhen the handle 211 is held in the desirable upright orientation, thetreatment may proceed uninterrupted. However, if the handle 211 movedout of its desired orientation, the ball may be configured to roll outof position and trigger a visual and/or auditory alarm to alert theuser. In another variation, an electronic gyroscopic sensor may be usedto maintain the handle 211 in the desired orientation for treatment.

FIG. 22A shows an example of one variation of a design of a system whichmay be used to deploy the balloon 174 into the uterus UT after properlysetting the depth of the uterine cavity (or some other anatomicalmeasurement). The elongate shaft 170 may have the balloon 174 attachedalong or near the distal end of the shaft 170 via a clamp or O-ring 171placed along the outside of the shaft 170. One or more indicators 173along the outer surface of the cannula may correspond to clinicalmeasurements of the uterine length which may be measured by theclinician prior to a cryoablative procedure. With the measured uterinecavity known, the balloon 174 may be adjustably clamped along the lengthof the shaft 170 at any one of the indicators 173 which may correspondto the measured cavity length. With the balloon 174 suitably clamped inplace, it may be pushed into the shaft lumen, as shown in FIG. 22B,using a pusher or some other instrument for delivery into the uterus UT.The elongate shaft 170 and balloon 174 may then be introduced into theuterus UT where the balloon 174 may be deployed from the shaft 170 andhaving a suitable length which may correspond to the particular anatomyof the patient.

The cooling probe positioned within the balloon 174 may be variouslyconfigured, as described above, and may include further variations. Asillustrated in the perspective and side views of FIGS. 23A and 23B,respectively, the cooling probe assembly 220 in this variation maycomprise an exhaust catheter 222 which may define a lumen 224therethrough. While the diameter of the exhaust catheter 222 may bevaried, its diameter may range anywhere from, e.g., 4.5 to 4.75 mm. Theexhaust catheter 222 may be formed from various materials, such asextruded polyurethane, which are sufficiently flexible and able towithstand the lowered treatment temperatures. The distal end of thecatheter 222 may have an atraumatic tip 226 which may be clear and/orwhich may also define a viewing window or opening through which animaging instrument such as a hysteroscope 246 may be positioned. One ormore supporting members or inserts 228, e.g., made from a polymer suchas polysulfone, may be positioned throughout the length of the lumen 224to provide structural support to the catheter 222 and to prevent itscollapse. The inserts 228 have a relatively short length and define achannel therethrough through which a probe support 230 (e.g., flat wire,ribbon, etc.) may extend. The probe support 230 shown in this variationmay comprise a flat wire defining one or more notches 232 along eitherside which may lock with one or more of the inserts 228 via insertsupports 240 to stabilize the probe support 230.

The probe support 230 itself may be fabricated from a material such asstainless steel and may have a thickness of, e.g., 0.008 in. The probesupport 230 may be supported within the lumen 224 via the inserts 228such that the probe support 230 separates the lumen 224 into a firstchannel 242 and a second channel 244 where the cooling lumens 236 may bepositioned along the probe support 230 within the second channel 244while the first channel 242 may remain clear for the optional insertionof a hysteroscope 246. In the event that a hysteroscope 246 is insertedwithin first channel 242, the hysteroscope 246 may be advancedselectively along the catheter lumen 224 for visualizing the surroundingtissue or the hysteroscope 246 may be advanced through the length of thecatheter 222 until it is positioned within a scope receiving channel 238defined within the catheter tip 226.

Because of the thickness of the probe support 230 relative to its width,the probe support 230 may be flexed or curved in a single plane, e.g.,in the plane defined by the direction of flexion 254 shown in FIG. 23B,while remaining relatively stiff in the plane transverse to the planedefined by the direction of flexion 254. This may allow for the probe220 to be advanced into and through the patient's cervix CV and into theuterus UT while conforming to any anatomical features by bending alongthe direction of flexion 254 (e.g., up to 90 degrees or more) but mayfurther allow the probe 220 to maintain some degree to rigidity andstrength in the transverse plane. Additionally and/or alternatively, thecatheter 222 may be actively steered along the direction of flexion 254,e.g., via one or more pullwires, to allow for positioning orrepositioning of the catheter 222 within the balloon 174 to facilitatefluid distribution and/or visualization.

The probe 220 may further include one or more cooling lumens 236 whichare positioned along the probe support 230 within the second channel244. In this example, at least two cooling lumens are used where a firstcooling lumen may extend through the probe 220 and terminate at a firstcooling lumen termination 248 near the distal tip 226 and a secondcooling lumen may also extend through the probe 220 adjacent to thefirst cooling lumen and terminate at a second cooling lumen termination250 at a location proximal to the first termination 248. The terminationpoints may be varied along the length of the probe 220 depending uponthe desired length of the active cooling portion 252 of the probe 220,which may extend from the distal tip 226 to a length ranging anywherefrom, e.g., 2 to 14 cm, along the probe length.

The cooling lumens 236A, 236B may be fabricated from any number ofmaterials suitable to withstand the low temperature fluids, e.g.,Nitinol, polyimide, etc. Moreover, the internal diameter of the coolinglumens may be made to range anywhere from, e.g., 0.010 to 0.018 in. Incertain variations, the cooling lumens may have an outer diameter of,e.g., 0.020 in., and an internal diameter ranging from, e.g., 0.016 to0.018 in., with a wall thickness ranging from, e.g., 0.002 to 0.004 in.

Because the cooling lumens 236 are located along the second channel 244,as separated by the probe support 230, one or more windows or openings234 may be defined along the length of the probe support 230 to allowfor the passage of any cryoablative fluid to pass through the openings234 and to then directly exit the catheter 222 through the openings 260defined along the catheter 222 body (as described below) and into theballoon interior. Alternatively, the cryoablative fluid may insteadproliferate through the entire lumen 224 defined by the catheter 222before exiting the catheter 222 body. These openings 234 may be cut-outsthrough the probe support 230 and may number anywhere from zero openingsto six or more, as shown, and they may be configured in any number ofsizes and shapes. Moreover, these openings 234 may be distributed in anyspacing arrangement or they may be uniformly spaced, e.g., 0.320 in.,depending upon the desired cooling arrangement.

The number of cooling lumens 236 may also be varied to number more thanthree lumens terminating at different positions along the active portion252. Additionally, the activation of the cooling lumens for spraying orintroducing the cryoablative fluid may be accomplished simultaneously orsequentially from each of the different cooling lumens depending uponthe desired ablation characteristics. While the cooling lumens maysimply define a distal opening for passing the fluid, they may beconfigured to define several openings along their lengths to furtherdistribute the introduction of the cryoablative fluid. The openings 260along the catheter body 222 for venting the cryoablative fluid into theballoon 174 are omitted from FIG. 23A only for clarity purposes but areshown in further detail in the following FIG. 24.

As the cryoablative fluid is initially introduced into the catheterlumen 242, the exhaust catheter 222 may also define one or more openingsto allow for the cryoablative fluid to vent or exhaust from the catheterinterior and into the interior of the balloon 174. As shown in theperspective view of FIG. 24, one or more openings 260 are illustrated toshow one example for how the openings 260 may be defined over the bodyof catheter 222. The openings 260 may be positioned along a single sideof the catheter 222 or they may be positioned in an alternatingtransverse pattern, as shown, to further distribute the cooling fluidthroughout the balloon interior. In either case, the positioning of theopenings 260 may be varied depending upon the desired cryoablationcharacteristics.

A cross-sectional end view of the cooling probe assembly 220 is shown inFIG. 25A illustrating the relative positioning of supporting insert 228attached to the probe support 230 within the catheter 222. The twocooling lumens 236A, 236B are illustrated adjacently positioned alongthe probe support 230 although they may be positioned elsewhere withinthe catheter 222 and may also number one lumen or greater than twolumens. Moreover, an optional hysteroscope 246 is also illustratedpositioned within the catheter 222 along the probe support 230. An endview of the distal tip 226 is also illustrated in FIG. 25B showing onevariation where the distal tip 226 may define a viewing window 270through which the hysteroscope 246 may be advanced for visualizingwithin the balloon 174 and uterus UT. In other variations, the viewingwindow 270 may be omitted and the distal tip 226 may be transparent forallowing visualization directly through the tip 226 by the hysteroscope246.

With such an arrangement of the cooling probe assembly 220 positionedwithin the balloon 174 (as illustrated above in FIG. 21B), the assembly210 may be used to treat the surrounding uterine tissue in closeconformance against the balloon 174 exterior surface. Introduction ofthe cryoablative fluid, e.g., nitrous oxide, through the cooling probe220 may allow for the ablation of the surrounding tissue to a depth of,e.g., 4 to 8 mm.

One example for a treatment cycle using a two cycle process may includethe introduction of the cryoablative fluid for a treatment time of twominutes where the surrounding tissue is frozen. The fluid may bewithdrawn from the balloon 174 and the tissue may be allowed to thawover a period of five minutes. The cryoablative fluid may be thenreintroduced and the tissue frozen again for a period of two minutes andthe fluid may then be withdrawn again to allow the tissue to thaw for aperiod of five minutes. The tissue may be visually inspected, e.g., viathe hysteroscope 246, to check for ablation coverage. If the tissue hasbeen sufficiently ablated, the assembly 210 may be removed from theuterus UT, otherwise, the treatment cycle may be repeated as needed. Inother alternatives, a single cycle may be utilized or more than twocycles may be utilized, as needed, to treat the tissue sufficiently.Furthermore, during the treatment cycle, a minimum pressure of, e.g., 40to 80 mm Hg, may be optionally maintained by the cryogenic liquid or bya gas (e.g., air, carbon dioxide, etc.) to keep the balloon 174 anduterus UT open.

In yet another alternative, aside from having a catheter 222 made as anextruded lumen, the catheter may be formed into tubing 201 such as ahypotube fabricated from a material such as, e.g., stainless steel,nitinol, etc. A tubing 201 formed from a metal may provide additionalstrength to the catheter and may remove the need for any inserts tomaintain a patent lumen. To increase the flexibility of the tubing 201,one or more slots 203 may be formed or cut along the body of the tubing201, as shown in the example of FIG. 26A, which illustrates aperspective view of tubing 201 having one or more slots 203 cuttransversely relative to the tubing 201. Aside from increasedflexibility, the slots 203 may be aligned to provide for preferentialbending or curvature along predetermined planes by the tubing whileinhibiting the bending or curvature along other planes, e.g., planestransverse to the bending plane, similar to the preferential bending orcurvature provided by the probe support 230.

The ends of the slots 203 may be formed to provide a separation 205between the ends of the slots 203. FIG. 26B shows another variationwhere each of the transverse slots 203 may have a strain relief feature207 formed at the distal ends of each slot 203 such that bending of thetubing 201 over the slotted region may occur with reduced stressimparted to the slots 203 and tubing 201. An additional feature mayinclude optional tabs 209 which may be formed along the body of thetubing 201 to extend internally for holding a cooling lumen within thelumen of the tubing 201.

Another variation is shown in FIG. 26C which shows transverse slots 203formed along the body of the tubing 201 where the slots 203 may beformed in an alternating pattern with respect to one another. FIG. 26Dshows yet another variation where angled slots 211 may be formedrelative to tubing 201. FIG. 26E shows another variation having one ormore serpentine slots 213 for preventing pinching where a distal end ofeach slot 213 may have a transverse slot 215 formed. FIG. 26F showsanother variation where one or more slots 217 having a transverse andlongitudinal pattern may be formed along tubing 201.

FIG. 26G shows another variation where a transverse slot 219 may have alongitudinal slot 221 formed at its distal end. FIG. 26H shows yetanother variation where one or more tapered slots 223 may be formedalong tubing 201. FIG. 26I shows another variation where a transverseslot 219 may have a longitudinal slot 221 formed where each of thelongitudinal slots 221 may be aligned longitudinally along the body oftubing 201. FIG. 26J shows another variation where transverse slots 219may have longitudinal slots 223 aligned adjacent to one another andhaving rounded ends. FIG. 26K shows another variation where either acurved serpentine slot 225 or an angled slot 227 may be formed along thetubing 201. Alternatively, both curved serpentine slot 225 and angledslot 227 may both be formed. Another variation shows tubing 201 having aplurality of slots 229 formed into a lattice structure over the body oftubing 201.

Aside from utilizing a continuous body of tubing 201 for the length ofthe cooling probe, discrete tubing reinforcing ring 231 may instead beformed from tubing 201. FIG. 27A shows an example where a plurality ofreinforcing rings 231 may be separated into discrete ring elements andattached to one another in a linear manner with one or more longitudinalbeam members 233 which may be attached to each reinforcing ring 231 atan attachment point 235, e.g., weld, adhesive, etc. One or more of thereinforcing rings 231 may be formed to have, e.g., a bent-in tab 237,for supporting beam 233 rather than utilizing a weld, adhesive, etc., asshown in the detail perspective view of FIG. 27B. The assembly of thereinforcing ring 231 and beams 233 may be covered with a membrane orother covering to form a uniform structure.

An example of a covering which may be used is shown in the end view ofFIG. 28A which shows a portion of tubing 201 or reinforcing ring 231 andcooling lumens 236 positioned on either side of tubing 201 orreinforcing ring 231. A heat shrink 241 material may be placed over theprobe assembly while maintaining clearance for openings 239 to allow fordelivery of the cryoablative fluid.

Another variation is shown in the cross-sectional end view of FIG. 28Bwhich shows the tubing 201 and respective cooling lumens 236 positionedwithin an insert 243 which define insert openings 245 for introducingthe cryoablative fluid. Yet another variation is shown in theperspective view of FIG. 29 which may incorporate a wound spring 247which may be tightly wound or packed to provide flexibility and tofurther provide a lumen 249 for the exhaust. One or more inserts 243 maybe positioned longitudinally along the length of the spring 247 and thecooling lumens 236 may be routed through the spring 247 and coupled toeach insert 243.

Another variation is shown in the partial cross-sectional side view ofFIG. 30A which illustrates how one or more inserts 243 may each define astep 251 for securement to the spring 247. The entire assembly may thenbe covered by a covering 253, e.g., flexible extrusion. Each of theinserts 243 may remain uncovered by either the spring 247 or covering253 to ensure that the cryoablative fluid has an unhindered pathway tothe balloon interior. FIG. 30B shows another variation where each of theinserts 243 may define a respective receiving channel 257 on either sideof the insert 243 for securement to the spring 247. An example of acooling lumen 236 is shown attached to each of the inserts 243 via anattachment 255, e.g., weld, adhesive, etc.

Aside from increasing the flexibility of the tubing or cooling probe,the cooling lumen may be configured to increase its flexibility as well.An example is shown in FIG. 31 which shows a portion of a cooling lumenwall 261 having a plurality of pivoted attachments 263. Such anarrangement may allow for each segment of the cooling lumen wall 261 topivot such that the cooling lumen cumulatively provides sufficientflexibility to bend and curve as the cooling probe assembly is advancedand positioned within the uterus. Such a cooling lumen may beincorporated into any of the probe variations described herein.

Another example of a cooling probe assembly is illustrated in theperspective view of FIG. 32 which shows discrete embedded insert 265 andone or more cooling lumens 236 attached to each respective insert 265covered with a covering 267. In this example, the covering 267 may beimplemented without any additional features or structures. FIG. 33 showsyet another example where individual inserts 265 may be aligned andcoupled with one or more beams 233, as previously described. Anadditional sliding joint 269 may be attached or integrated along eachinsert 265 to provide support to one or more cooling lumens 236 whichmay be translatably positioned through each aligned sliding joint 269.

Yet another variation is illustrated in the side view of FIG. 34 whichshows a wound spring element 271 having one or more cooling lumens 236aligned longitudinally along the spring element 271. The one or morecooling lumens 236 may be attached to the spring element 271 viaconnectors 273 which may be aligned relative to one another to receiveand secure the cooling lumens 236. A covering may be optionally securedover the spring assembly.

FIG. 35 shows another variation where spring element 271 may incorporateone or more respective inserts 243. In this variation, the springelement 271 has the one or more cooling lumens 236 coupled to the springelement 271 itself. FIG. 36 shows yet another variation where the springelement 271 and the one or more cooling lumens 236 (which may be coupleddirectly to the spring element 271), may have an optional secondarylumen 275 passing through the spring element 271 and optionally attachedto the spring itself. The second lumen 275 may be sized for receiving aninstrument such as a hysteroscope 246. The second lumen 275 may providea redundant liquid or gas pathway should the primary lumen becomepartially or fully obstructed. The redundant pathway may exist betweenthe optional instrument, e.g. hysteroscope, and primary lumen or withinthe full second lumen 275.

The secondary lumen 275 may be shown in various cross-sections in theend views of FIG. 37. A first variation is illustrated shown secondarylumen 275 having a circular cross-sectional area with a hysteroscope 246passed through a center of the lumen 275. A second variation isillustrated where the hysteroscope 246 may be passed along a side of thelumen 275 and a third variation is illustrated showing a secondary lumen275A having an elliptical cross-sectional area.

Another variation for a cooling probe assembly is shown in theperspective views of FIGS. 38A to 38C. In this variation, the catheterbody 222 is omitted for clarity purposes only but a main delivery line280 is shown extending through the catheter with at least two sidedelivery lines 282, 284 positioned near the surface of the catheterbody, as shown in FIG. 38A. The main delivery line 280 may be in fluidcommunication with the side delivery lines 282, 284 via a junction 288,shown in FIG. 38B, near or within the distal tip 226. As thecryoablative fluid is introduced into the main delivery line 280, thefluid in the side delivery lines 282, 284 may be vented through one ormore openings 286 defined therealong for venting through and into thecatheter and balloon interior. An optional mandrel 290, as shown in FIG.38C, may be slidingly fitted within each of the side delivery lines 282,284 and actuated automatically along with the retraction of the sheath212 or by the user to slide along the interior of one or both sidedelivery lines 282, 284 to selectively obstruct the openings 286 andthereby control the amount of cryoablative fluid delivered. As shown,one or more obstructed openings 292 may be blocked by the mandrel 290 byselectively sliding the mandrel 290 accordingly. In other variations,rather than using mandrels inserted within the delivery lines 282, 284,a sheath or mandrel placed over the delivery lines 282, 284 may be usedinstead to achieve the same results.

As described above, the retraction of the mandrel 290 may be optionallyactuated to follow along with the retraction of the sheath 212.Accordingly, the retraction of the mandrel 290 may occur simultaneouslywith the retraction of the sheath 212 but the retraction may optionallyoccur at different rates as the amount of cryoablative fluid deliveredmay be related to the length of the uterine cavity to be treated. Forinstance, a sheath retraction of, e.g., 7 cm, may result in 10unobstructed openings 286 whereas a sheath retraction of, e.g., 4 cm,may result in, e.g., 6 unobstructed openings 286.

Another variation of the cooling probe assembly is illustrated in thedetail cross-sectional side view of FIG. 39. In this variation, a singlemain delivery line 280 may pass through and into communication withdistal tip 226. Rather than having the side delivery lines 282, 284coupled directly to the main delivery line 280, each respective line maybe coupled to a common chamber 301 defined within the distal tip 226.Such an assembly may be used with alternative variations of the exhaustlumen 303 as shown in one example in the cross-sectional end view ofFIG. 40A. In this example, the exhaust lumen 303 may be formed to havean indented cross-sectional area to accommodate the side delivery lines282, 284. Alternatively, the exhaust lumen 303 may be shaped to have anelliptical cross-sectional area instead, as shown in FIG. 40B.

In yet another alternative, the cooling lumens may be formed to have asingle introduction or infusion line 305 and a single delivery line 307where the delivery line 307 may be in fluid communication directly withthe introduction or infusion line 305 through the distal tip 226, asshown in the cross-sectional side view of FIG. 41. The infusion line 305and delivery line 307 may be formed as separate lines or they may formedas a single continuous line where the infusion line 305 enters distaltip 226 and is curved to redirect the ablative fluid proximally throughthe delivery line 307. In this variation, as in the previous variations,a translatable mandrel 290 may be slidably positioned within thedelivery line 307 or optionally along an outer surface of the deliveryline 307 to selectively obstruct the openings 286 defined along the line307. In other variations, one or more openings may also be optionallyaligned along the infusion line 305 in addition to the openings 286along delivery line 307. Moreover, the mandrel 290 may be actuated toslide (either at the same or different rate) along with the retractionof the sheath. FIG. 42 illustrates an example where the cooling probeassembly may be introduced into the interior of balloon 174 whendeployed within the uterus UT. Alternatively, the balloon 174 may beattached directly along an outer surface of the cooling probe assemblyitself. The expanded length of balloon 174 may be fixed along the outersurface of the cooling probe assembly proximal to the distal tip or itmay be optionally adjustable via the positioning of the outer sheath. Asshown, the introduction line 305 may introduce the cryoablative fluidalong the cooling probe assembly where it may then be flowed proximallyalong the delivery line 307 for introduction into the interior of theballoon 174. As the cryoablative fluid is introduced, a slotted tube 311having one or more directional slots 313 may be used to optionallydirect the flow of the cryoablative fluid into the balloon interior.

FIGS. 43A and 43B illustrate additional variations for selectivelycontrolling the configuration of the hole directions along the sidedelivery lines to optionally control appropriate ablation depths andtapering, as needed or desired. In the variation of FIG. 43A, theadjacent side delivery lines 282, 284 from the distal tip 226 may beconfigured such that openings 300 are configured in an up/downconfiguration, openings 302 are configured in an down/up configuration,openings 304 are configured in an left/right configuration, openings 306are configured in an up/down configuration, and openings 308 areconfigured in an down/up configuration. The hole directions ofup/down/left/right are relative to the figures shown and are presentedfor illustrative purposes.

Likewise, the variation shown in FIG. 43B illustrates how the adjacentside delivery lines 282, 284 may be configured such that openings 310are configured in an up/down configuration, openings 312 are configuredin an left/right configuration, openings 314 are configured in andown/up configuration, openings 316 are configured in an left/rightconfiguration, and openings 318 are configured in an up/downconfiguration. These variations are illustrated as exemplary variationsand other variations of hole directions may be accomplished as desired.

Aside from the positioning of the fluid openings, the catheter body 222itself may optionally incorporate a skived viewing window 320, as shownin the side view of FIG. 44, to facilitate visualization of thesurrounding balloon 174 and tissue by the hysteroscope 246 which may beadvanced into proximity to the window 320 or entirely through asdesired.

As previously described, the balloon 174 may be expanded within theuterus UT and particularly into the uterine cornu UC by an initial burstof gas or liquid. Other mechanisms may also be used to facilitate theballoon expansion. One variation is shown in FIG. 45 which illustrates aballoon 174 having one or more supporting arms 330A, 330B extending froma support 334 which may be deployed within the balloon 174. Thesupporting arms 330A, 330B may be variously configured although they areshown in this example in a Y-configuration. Each of the distal ends ofthe arms may extend from a linear configuration into the expandedY-configuration, e.g., via a biasing mechanism 332, which may bias thearms to extend once the sheath 212 is retracted. The distal ends of thearms 330A, 330B may extend into the tapered corners of the balloon 174to facilitate the balloon 174 expansion into the uterine cornu UC andmay also help to center the balloon 174 within the uterus UT.

FIG. 46 shows a partial cross-sectional side view of another variationof an expansion mechanism contained within the balloon 174 where one ormore supporting arms 342A, 342B may be mechanically actuated to extend,e.g., via a biasing mechanism, push/pull wires, etc. Moreover, the arms342A, 342B may be integrated into the design of the cooling probe 340 asan integrated assembly.

FIG. 47 shows a partial cross-sectional side view of another variationwhere the supporting arms 350A, 350B may also integrate one or moreopenings 352 for the infusion of the cryoablative fluid. In this examplethe arms 350A, 350B may be integrated with the cooling probe 340 orseparated. In either case, the inclusion of the openings 352 mayfacilitate the distribution of the fluid into the balloon 174 interior.

FIG. 48 shows yet another variation where the supporting arms 360A, 360Bmay be incorporated into elongate channels or pockets 362A, 362B definedalong the balloon 174 itself. In this and other variations shown, thesupporting arm members may optionally integrate the one or more openingsfor cryoablative fluid delivery and may also be integrated into elongatechannels as practicable.

FIGS. 49A and 49B show cross-sectional side views of yet anothervariation of a cooling probe which utilizes a single infusion line incombination with a translatable delivery line. To accommodate varioussizes and shapes of uterine cavities, the cooling probe may have asliding adjustment that may be set, e.g., according to the measuredlength of the patient's uterine cavity. The adjustment may move alongthe sheath along the exhaust tube as well as the delivery line withinthe infusion line. The sheath may constrain the liner 174 and alsocontrol its deployment within the cavity.

In this variation, an infusion line 239 (as described above) may passfrom the handle assembly and along or within the sheath and into theinterior of liner 174. The infusion line 239 may be aligned along theprobe 178 such that the infusion line 239 is parallel with alongitudinal axis of the probe 178 and extends towards the distal tip367 of the probe 178. Moreover, the infusion line 239 may be positionedalong the probe 178 such that the line 239 remains exposed to thecorners of the liner 174 which extend towards the cornua. With theinfusion line 239 positioned accordingly, the length of the line 239within the liner 174 may have multiple openings formed along its lengthwhich act as delivery ports for the infused cryogenic fluid or gas. Aseparate translating delivery line 365, e.g., formed of a Nitinol tubedefining an infusion lumen therethrough, may be slidably positionedthrough the length of the infusion line 239 such that the delivery line365 may be moved (as indicated by the arrows in FIG. 49A) relative tothe infusion line 239 which remains stationary relative to the probe178.

The openings along the length of the infusion line 239 may be positionedsuch that the openings are exposed to the sides of the interior of theliner 174, e.g., cross-drilled. As the cryogenic fluid or gas isintroduced through the delivery line 365, the infused cryogenic fluid orgas 369 may pass through the infusion line 239 and then out through theopenings defined along the infusion line 239. By adjusting thetranslational position of the delivery line 365, the delivery line 365may also cover a selected number of the openings resulting in a numberof open delivery ports 361 as well as closed delivery ports 363 whichare obstructed by the delivery line 365 position relative to theinfusion line 239, as shown in the top view of FIG. 49B.

By translating the delivery line 365 accordingly, the number of opendelivery ports 361 and closed delivery ports 363 may be adjusteddepending on the desired treatment length and further ensures that onlydesired regions of the uterine tissue are exposed to the infusedcryogenic fluid or gas 369. Once the number of open delivery ports 361has been suitably selected, the infused cryogenic fluid or gas 369 maybypass the closed delivery ports 363 obstructed by the delivery line 365and the fluid or gas may then be forced out through the open deliveryports 361 in a transverse direction as indicated by the infusion spraydirection 371. The terminal end of the infusion line 239 may beobstructed to prevent the distal release of the infused fluid or gas 369from its distal end. Although in other variations, the terminal end ofthe infusion line 239 may be left unobstructed and opened.

FIGS. 50A and 50B show top and perspective views of the expanded liner174 with four pairs of the open delivery ports 361 exposed in apposeddirection. Because the infused fluid or gas 369 may be injected into theliner 174, e.g., as a liquid, under relatively high pressure, theinjected cryogenic liquid may be sprayed through the open delivery ports361 in a transverse or perpendicular direction relative to the coolingprobe 178. The laterally infused cryogenic fluid 371 may spray againstthe interior of the liner 174 (which is contacted against thesurrounding tissue surface) such that the cryogenic liquid 371 coats theinterior walls of the liner 174 due to turbulent flow causing heavymixing. As the cryogenic liquid 371 coats the liner surface, the sprayedliquid 371 may absorb heat from the tissue walls causing rapid coolingof the tissue while also evaporating the liquid cryogen to a gas formthat flows out through the cooling probe 178. This rapid cooling andevaporation of the cryogenic liquid 371 facilitates the creation of afast and deep ablation over the tissue. During treatment, thetemperature within the cavity typically drops, e.g., −89° C., within 6-7seconds after the procedure has started. While the interior walls of theliner 174 are first coated with the cryogenic liquid 371, the cryogenicliquid 371 may no longer change phase as the procedure progresses.

While four pairs of the open delivery ports 361 are shown, the number ofexposed openings may be adjusted to fewer than four pairs or more thanfour pairs depending on the positioning of the delivery line 365 andalso the number of openings defined along the infusion line 239 as wellas the spacing between the openings. Moreover, the positioning of theopenings may also be adjusted such that the sprayed liquid 371 may sprayin alternative directions rather than laterally as shown. Additionallyand/or alternatively, additional openings may be defined along otherregions of the infusion line 239. For instance, one or more openings361′, e.g., one to three holes or more, may be added along the length ofthe infusion line 239 such that the openings directly face the portionof the liner 174 placed against the anterior portion of the contactedtissue, as shown in the perspective view of FIG. 50C.

Prior to or during treatment, the positioning of the cooling probe 178within the interior of the liner 174 and the uterus may be determinedthrough various mechanisms. Visualization may be optionally provided byuse of hysteroscopy, endoscopy, fluoroscopy, or ultrasound or other moreinvasive modalities. However, other variations for determining thecooling probe 178 position may include use of a transmitter 381, e.g.,light, ultrasound, etc., which may be placed on the distal tip 367 ofthe probe 178, as shown in the perspective view of FIG. 51A.

In the event that a light 381 such as an LED light is placed upon thedistal tip 367, the user may simply visually monitor the patient for thetransmission of the light through the tissue and skin of the patient todetermine whether the tip 367 is properly positioned within the uterusor the peritoneal cavity depending on where the light is emitteddirectly through the body. In another variation, a sensor or receiver383 may be placed upon the distal tip 367 adjacent to the transmitter381. As the transmitter 381 emits a light or ultrasound signal 385, thesignal 385 may reflect off the surrounding tissue surface (and throughthe liner 174). Depending on the wavelength of the reflected signalscollected by the receiver 383, a processor or microcontroller can beused to determine the general color of the tissue in front of the end ofthe probe as the inner wall of the uterus, intestine, and bladder shouldall have distinct color signatures.

In yet another variation, one or more transmitters 387, e.g., light,ultrasound, etc., may be placed along the probe 178 along oppositesurfaces to facilitate determining the amount of cavity expansion, e.g.,during initial pre-treatment liner expansion. The transmitted signals391 may be emitted as discrete pulses of light which are returned asreflected signals 393 to corresponding sensors or receivers 389 whichare adjacent to the transmitters 387. By measuring the time it takes forthe reflected signals 393 to return to the sensors or receivers 389, theprocessor or microcontroller can determine the amount of cavityexpansion which has occurred. The transmitters and/or sensors/receiversmay be incorporated in any of the variations of the devices and methodsdescribed herein.

Once a cryoablation treatment procedure has been completed and theinterior of the liner is vented, the device may be removed from thepatient body. To facilitate the removal of the liner 174 from thetreated tissue surface, negative pressure may be applied to the interiorof the liner 174 to quickly remove the discharged cryogenic fluid or gasas well as to help pull the liner 174 away from the tissue surface.Removing the liner 174 from the tissue surface may be relatively easywhen the removal force is normal to the tissue surface. Hence, use ofnegative pressure or a suction force at the end of an ablation proceduremay facilitate the removal or peeling of the liner 174 from the uterinetissue surface.

The pump which is used to introduce air initially into the linerinterior may be used to also remove the discharged cryogenic fluid orgas particularly if the pump (such as pump 225 shown above in FIG. 21G)is configured as a reversible pump, e.g., connected to H-bridgecircuitry which may allow for the polarity of the voltage on the pump tobe reversed which will allow for the reversal of the flow direction ofthe pump. Another variation may utilize a separate pump which isconfigured to draw a suction force upon the liner interior separate fromthe pump used to introduce air into the liner.

Yet another variation may utilize a non-reversible pump 395 which isfluidly coupled to a 5-port, 2 position, 4-way valve 405 which allowsfor the pressured pump output 397 to be connected to the exhaust/liner407 through output line 401 and through liner line 415 within valve 405.A first switch 409 within the valve 405 may be switched to fluidlycouple the output line 401 with the liner line 415. The negativepressure pump input 399 may be opened to the ambient air 419 throughambient line 417 within the valve 405 for initially expanding the liner174, as shown in the schematic illustration of FIG. 52A. The ambient air419 may be fluidly coupled to the input line 403 via second switch 411within the valve 405.

When the ablation procedure has been completed and the liner 407 to bevented and collapsed, the valve 405 may be switched such that firstswitch 409 fluidly couples output line 401 to ambient line 413 andsecond switch 411 switches to fluidly couple the liner 407 to liner line415 and input line 403, as shown in the schematic illustration of FIG.52B. The fluid and/or gas within the liner 407 may be drawn out by thenegative pressure created within input line 403 which may then force thedischarged fluid or gas through output line 401, through ambient line413 within valve 405, and out as exhausted fluid or gas 421. Thus, asingle directional pump 395 may be used for both inflation and deflationwith the valve 405.

Yet another variation is shown in the schematic diagrams of FIGS. 53A to53C which also illustrates the use of a non-reversible pump 395 for bothinflation and deflation. In this variation, the pump output line 401 mayincorporate a first 3-way valve 425 and the pump input line 403 mayincorporate a second 3-way valve 427. The first and/or second valves425, 427 may comprise, e.g., 3-way solenoid valves, which may remainunpowered with both valves 425, 427 connecting the pump 395 to theambient environment through respective ambient lines 429, 431, as shownin FIG. 53A. The configuration shown may keep any fluid or gas withinthe liner 407 from being pumped or leaked to the environment.

If the liner 407 is to be evacuated, the first valve 425 may be actuatedor energized such that the pump output line 401 is fluidly connected tothe ambient line 429 and the second valve 427 may be actuated orenergized to fluidly couple the liner 407 with the pump input line 403,as shown in FIG. 53B. With the pump 395 actuated, the input line 403 maydraw a negative pressure to suction out the fluid or gas within liner407 while the pump output pushes air or the suctioned fluid or gas outthrough ambient line 429.

If the liner is to be initially expanded and/or the cryogenic fluid orgas is to be to introduced into the liner 407 for treatment, the firstvalve 425 may be actuated or energized to fluidly couple the output line401 from the pump 395 to the liner 407 while the second valve 427 may beactuated or energized to fluidly couple the pump input line 403 with theambient line 431, as shown in FIG. 53C. Moreover, the actuation of thefirst and second valves 425, 427 may be coordinated such thatsimultaneous or individual actuation of the valves is controlled by aprocessor. Alternatively, one or both valves 425, 427 may be controlledmanually by the user. As above, this valve configuration may be usedwith any of the different liner, probe, handle assembly, or treatmentmethods described herein.

Turning now to the liner itself, the liner may be formed to have, e.g.,a nominal 0.0012 in. thick flexible membrane such as pellethane. Theliner 174 may be optionally formed as a composite from one or moresheets of material, e.g., two sheets of membrane which are RF welded.When laid out in a flattened shape, the liner 174 may shaped in amanner, as shown in the top view of FIG. 54A, which allows the liner 174to inflate or expand into a contoured shape which conforms closely to auterine cavity, as shown in the perspective view of FIG. 54B. FIG. 54Ashows one example of a flattened liner 174 which gently tapers from theopening to a curved shape forming a first curved portion 435A and asecond curved portion 435B opposite to the first curved portion 435A.The liner 174 may hence taper gently from a first width W1, e.g., about2.4 in., down to a second width W2, e.g., about 0.3 in., over a lengthL1 of, e.g., about 3.5 in. The neck may form a length L2, e.g., about0.9 in.

The region between each of the first and second curved portions 435A,435B may also be curved to have a radius R1 of, e.g., about 3.5 in.,while curved portions 435A, 435B may also be curved to each have aradius R2 of, e.g., about 0.3 in. The portion of the liner proximal tothe portions 435A, 435B may also have a radius R3, e.g., about 1.1 in.,and an oppositely radiused portion of radius R4, e.g., about 8.0 in. Theregion between the liner 174 and neck may further have a radius R5,e.g., about 0.2 in.

The liner 174 itself may be formed to have a uniform thickness over theentire liner. Alternatively, different portions of the liner 174 mayalso be formed to have differing thicknesses depending upon the desireddegree of treatment along differing portions of the liner 174. Forinstance, the liner 174 may have varying regions of thickness T1, T2, T3along proximal portions of the liner relative to distal portions of theliner.

Moreover, to facilitate smooth retraction of the sheath and consistentdeployment, the liner 174 may be pleated to fold and collapse in aconsistent manner, as shown in the perspective view of FIG. 54C. Theliner 174 may be pleated, e.g., using a fixture during manufacturing.

As previously described, the probe 178 may be advanced into and throughthe patient's cervix CV and into the uterus UT while conforming to anyanatomical features by bending along an anterior direction of flexion445 or posterior direction of flexion 447 (e.g., up to 90 degrees ormore) but may further allow the probe 178 to maintain some degree torigidity and strength in the transverse plane. The probe 178 mayaccordingly have a plurality of cut patterns 441, e.g., laser-cut, alongthe anterior and posterior surfaces of the probe 178, as shown in theside and top views of FIGS. 55A and 55B. These cut patterns 441 may becut partially through the probe 178 along opposing surfaces, e.g., in analternating manner, and may further define portions of removed material443 along the ends of each cut pattern 441. In addition to the cutpatterns 441, one or more H-slots 449 may also be cut periodicallyalong, e.g., the anterior surface of the probe 178 to allow foranchoring locations for the infusion line 239.

An example is illustrated in the perspective view of FIG. 55C whichshows a probe 178 having multiple probe sections 453A, 453B, 453C, 453D(e.g., four sections in this variation) separated by H-slots 449. One ormore anchors 451 (e.g., collars, clips, etc.) may couple the infusionline 239 to the probe 178 along its anterior surface via the anchors 451secured to the H-slots 449, as shown.

Aside from the liner or balloon itself and the use of balloons forobstructing the os, internal os, and/or external os, as described above,balloons or inflatable liners may also be used to insulate the cryogenicfluid during delivery into the balloon to protect the surrounding tissuestructures which are not to be ablated, such as the cervix CV. Onevariation is illustrated in the perspective assembly view of FIG. 56Awhich shows a cervical protection assembly having an inner sheath 461(e.g., PTFE or other polymer) which may be inserted within an outersheath 465 (e.g., double walled stainless steel). The inner sheath 461may have an inner sheath hub 463 at its proximal end which may securelycontact an outer sheath hub 467 also located at its proximal end. Withthe inner sheath 461 inserted entirely within outer sheath 465, theinner sheath 461 may prevent the liner 174 from inflating into contactagainst the outer double walled sheath 465.

As shown in the cross-sectional perspective view of FIG. 56B, the doublewalled outer sheath 465 may have an inner tubular member 471 and asurrounding outer tubular member 469 (e.g., stainless steel, polymer,etc.) forming an insulating annular gap or spacing 473 (e.g., 0.0115 in.spacing). In the event that the tubular members 469, 471 are made of apolymer, the tubular members may be made with a wall thickness of, e.g.0.00025 to 0.003. The distal end of the outer sheath 465 may have distaltip 475 to maintain the spacing between the tubular members of the outersheath 465. With the annular gap or spacing 473 and the presence of theinner sheath 461, the sheath assembly may provide thermal insulation forthe cervical region by insulating the surrounding tissue from thecryogenic fluid or gas passed through the infusion line 239 and from thecryogenic fluid or gas withdrawn through the inner sheath 461 from theliner 174.

While the annular gap or spacing 473 may have air within the spacingfunction as an insulator, the spacing may alternatively be evacuated ofair to provide for a vacuum insulator. In another alternative, activeflow of warmed or ambient temperature fluid (air or gas) may be includedbetween the inner and outer tubular members 469, 471 or insulativematerials may instead be placed within the gap or spacing (e.g.,inflatable balloons, spiral wound balloons, cotton, wool, syntheticfibers, Neoprene, etc.). In yet another alternative, additional tubularmembers may be incorporated to create multiple annular gaps.

Additionally and/or optionally, the temperature of the sheath 212 mayalso be monitored so that the temperature may be provided in a feedbackloop to a processor or microcontroller for ensuring the surroundingtissue (e.g., cervix) is maintained at a safe level. Accordingly, one ormore temperature sensors T, e.g., thermocouples, may be placed along thesheath 212, as shown in FIG. 56C, and in communication with theprocessor or microcontroller. The processor or microcontroller mayaccordingly be programmed with a feedback loop which could start, pause,or stop the delivery of the cryogenic fluid or gas based upon thetemperature (e.g. −89.5° C. for nitrous oxide) of the sheath 212.

In actuating and controlling the translation of the sheath 212 and probe178, the handle assembly 211 may further incorporate a sheath bearingtube 477 coupled to the sheath 212 assembly. FIG. 57 illustrates onevariation where the sheath bearing tube 477 slidingly pass through asheath bearing assembly 219 and then attached to a slider base blockassembly 221 which is positioned within the handle assembly 211. Theactuatable sheath control 223 may be attached to the slider base blockassembly 221 for advancing and retracting the slider base block assembly221 to control the positioning of the sheath 212 to ensure that thesheath 212 covers the cervical region during a treatment procedure.

FIG. 58 shows a detail perspective view of the connection between thesheath bearing tube 477 and slider base block assembly 221. One or twolinear rails 479 may be aligned adjacent to the sheath bearing tube 477within handle 211 to serve as bearing surfaces for the slider base blockassembly 221. Additionally, a receiving channel 481 may be defined alongthe anterior surface of the sheath bearing tube 477 to function as anaccess channel for the infusion line 239 into or along the sheathassembly. Accordingly, as the slider base block assembly 221 istranslated linearly along the rails 479, the sheath bearing tube 477 andinfusion line 239 may be advanced distally and/or proximally relative tothe probe 178 to control the relative positioning of the sheath 212.

As illustrated in the perspective views of FIGS. 59A and 59B, when theslider base block assembly 221 is advanced distally relative to thehandle assembly 211, the sheath 212 may be translated distally such thata nominal exposed length D1 of the probe 178 may be seen. (The liner 174is not shown for clarity only.) As the slider base block assembly 221 isadvanced proximally, the sheath 212 may be accordingly retracted toexpose the probe 178 further, as indicated by the exposed length D2. Thefull travel of the sheath and slider base block assembly 221 may rangeanywhere from, e.g., 1 cm to 8 cm or more, as measured from the distalend of sheath 212 to the distal end of the tip of probe 178. Thepositioning of the slider 221 and sheath 212 may be maintained via anynumber of locking or positioning mechanisms to ensure that the ablationlength is maintained during a treatment procedure. Hence, the locking ofthe slider 221 and sheath 212 may be accomplished by locking mechanisms,e.g., friction fitting, detention features such as notches along thelength of the slider travel, grabbing mechanism such as a brake betweenthe slider and handle, actuating features, etc.

By measuring the pressure decay within the liner 174 during treatment,the rate at which the cryogenic liquid is being converted to a gaseousstate may be determined since the lower the cavity pressure the lesscryogenic fluid is being converted from liquid to gas. One or moreoptional pressure sensing lines 485 may be incorporated along the probe178, as shown in the perspective view of FIG. 60. (A secondary line maybe provided for redundant measurement of the pressure.) The pressuresensing line 485 may have a pressure sensor 487 positioned along acutout window 489 defined along the probe 178 for monitoring thepressure internal to the liner 174 during treatment. The cutout window489 may be provided to prevent the ends of the pressure lines 485 fromcontacting the interior of the liner 174. The pressure lines 485 may berouted along the full length of the sheath 212 and the proximal ends ofthe lines 485 may be attached to connectors which connect to thepressure sensors via short silicone tube sections.

Additionally, the pressure sensing lines 485 and sensors 487 may also beused as safety feature for the system. The lines 485 and sensors 487 cantrigger the actuatable valve 237 which is fluidly coupled to thecryogenic line 235 (shown above in FIG. 21E) to close and stop the flowof the cryogenic fluid or gas in the event of pressures detected in theuterine cavity which are higher than expected.

FIG. 61 shows a partial cross-sectional of another variation where aninflatable balloon 370 may be located along the outside distal surfaceof sheath 212 for contacting against and directly insulating the cervixCV. The liner or balloon 370 may be filled with a gas or liquid such asair, water, carbon dioxide, etc. to act as an insulator to preventcontact between the delivered cryoablative fluid passing through theshaft 170 and the surrounding cervical tissue. The balloon 370 may beinflated prior to or during an ablation treatment and then deflated oncethe treatment has been completed to facilitate removal of the device.The size of the balloon 370 may be optionally varied, e.g., by thesheath placement location.

FIG. 62 shows a cross-sectional side view of another variation of aninflatable liner or balloon 380 located along the inside distal surfaceof sheath 212. In this variation, the balloon 380 may inflate toinsulate the cryoablative fluid from the cervical tissue. FIG. 63 showsanother variation where expandable foam 390 may be deployed via theouter sheath 212 for insulating against the cervix CV. FIG. 64 shows yetanother variation where a heating element 400 may be located along theinner or outer surface of the elongate shaft 170 for heating thesurrounding cervical tissue as the cryoablative fluid is deliveredduring treatment. FIG. 65 shows yet another variation where a ringballoon 410 may be inflated along either the sheath 212 or shaft 170 toeither insulate the surrounding cervical tissue or to ensure secureplacement of the shaft 170 and/or balloon 174 during treatment.

FIG. 66 shows a cross-sectional side view of yet another variation of asheath 411 which may be formed from, e.g., urethane having a thin wallof about 0.001 in., which may be doubled over and sealed such that thesheath 411 contains a volume of liquid or gas 413 such as saline, air,etc. The cooling probe assembly having the tubing 201 and balloon 174 inits collapsed state may also be seen. The sheath distal end 415 mayoptionally incorporate a deformable member such as an elastic orexpandable ring 417 contained circumferentially within the distal end415, as shown in the side view of FIG. 67A. Alternatively, a biasedcircular member such as a ring 419 comprised of a circularly-formedspring may be contained circumferentially within the distal end 415, asshown in FIG. 67B. With the sheath 411 positioned with its distal end415 distal to the tubing 201, the ring 417 may configure into a ringhaving a first diameter which at least partially covers the distalopening of the sheath 411. However, when the tubing 201 is advanced fromthe sheath 411, the ring 417 may stretch or deform into a second largerdiameter as it conforms to the outer surface of the tubing 201. Theenlarged ring 417 may accordingly form a stop or detent for preventingthe proximal over-withdrawal of the sheath 411 relative to the cervix CVas well as facilitating the positioning of the sheath 411 over thecervix CV to provide insulation during a procedure. As the outer sheath411 and enlarged ring 417 is positioned proximally along the tubing 201to secure a position of the ring 417 against cervical tissue, the sheathretraction may accordingly adjust an expanded length of the balloon 174within the uterus UT.

Moreover, since the positioning of the sheath 411 may also actuate andadjust a position of a mandrel 290 within the one or more lines 307 toselectively obstruct or open a selected number of openings 286 (asillustrated in FIG. 41), the single withdrawal and positioning of theouter sheath 411 may not only provide an adjustable securement of thedevice relative to the cervical tissue, but it may also correspondinglyadjust the balloon expanded length and further control the active lengthof the delivery line 307 via the mandrel 290 positioning. The sheathretraction and securement may be utilized not only in this variation,but in any of the variations shown and described herein, as practicable.

FIG. 68 shows another variation of a cervical protection balloon 421 mayhave a length, e.g., 4 to 8 cm, that may also be positioned along theoutside surface of the sheath 212 (as shown) or along the inside surfacefor placement against the cervical tissue. FIG. 69 shows across-sectional side view of yet another variation of a dual sheathassembly having an inner sheath 423 and an outer sheath 425 which arelongitudinally translatable relative to one another. An annular balloon427 may be attached to the distal ends of both the inner sheath 423 andouter sheath 425 such that the balloon 427 size and configuration may bealtered by the relative movement and positioning of the sheaths 423,425. FIGS. 70A and 70B show detail cross-sectional side views of anexample of an arrangement for several seals 429 which may be positionedbetween each respective sheath 423, 425. Corresponding o-ring seals 431may be incorporated into the seals 429 to provide for fluid-tightsealing. Also, a fluid line 433 may be passed through one or more seals429, as shown, to provide for inflation and deflation of the balloon 174or annular balloon 427.

Another variation is shown in the cross-sectional side view of FIG. 71which shows another dual sheath design where the annular balloon may becomprised of a confined balloon 441 having an expandable balloon portion443. The balloon, e.g., urethane, may be contained between eachrespective sheath 423, 425 while a doubled-over portion may bepositioned to extend from between the distal ends of the sheaths 423,425. As inflation fluid is introduced into the balloon, the portion ofthe balloon constrained between the sheaths 423, 425 may remaincollapsed but the unconstrained expandable balloon portion 443 mayexpand into an annular shape as shown.

FIG. 72 shows yet another variation where the sheath 445 may be formedto have a reinforcement member 447, e.g., wire, braid, mesh, etc.,integrated along its body to provide for added strength and spacebetween the sheath 445 and adjacent tissue. Any of the balloonembodiments described herein may be incorporated with the sheath 445 asshown.

FIG. 73 shows another variation of a sheath having an annular balloon449 positioned along the distal end of the inner sheath 423 whileconstrained by the distal end of the outer sheath 425. The balloon 449may be sized according to the relative positioning between the inner andouter sheaths.

FIGS. 74A and 74B show partial cross-sectional side views of yet anotherexample of an outer sheath 451 slidably positioned over tubing 201 wherethe distal end of outer sheath 451 may incorporate an integratedexpandable ring 453, e.g., elastomeric, foam, etc. As previouslydescribed in a similar embodiment, the expandable ring 453 may have afirst diameter which closes upon the distal end of tubing 201 when theouter sheath 451 is advanced distal to the tubing 201. As the outersheath 451 is retracted relative to tubing 201, the ring 453 may expandto a larger second diameter as it conforms to the outer surface of thetubing 201. The enlarged profile of the outer sheath 451 may thusfunction as a stop relative to the cervical tissue during a procedure.

FIG. 75 shows a similar variation where the expandable ring 453 mayincorporate one or more lubricious surfaces 455 to facilitate theretraction of outer sheath 451, e.g., by peeling the outer layerrelative to the inner layer, and the conformance of the ring 453relative to the tubing 201. FIG. 76 shows a side view of yet anothervariation where the outer sheath 451 may instead incorporate a discretering section 461 having the expandable ring 453 positioned relative tothe tubing 201. FIG. 77 shows yet another variation where the distal endof the tubing 201 may define a tapered distal end 463 to facilitate theexpansion of the expandable ring 453 when outer sheath 451 is retracted.

In yet another variation of the outer sheath, FIG. 78 shows anembodiment where the outer sheath 465 may have a radially expandableportion 467 formed near or at a distal end of the outer sheath 465.Prior to or during a procedure to secure a position of the outer sheath465 relative to the cervical tissue, the expandable portion 467 may beutilized rather than an inflatable balloon. The expandable portion 467may generally comprise one or more lengths of the outer sheath 465 beingreconfigurable along a pivotable or bendable portion such that as thedistal end of the outer sheath 465 is retracted relative to theremainder of the sheath 465, the one or more lengths may pivot andreconfigure into its radial configuration.

A linkage 475 (such as wire, rod, string, ribbon, etc.) may be coupledto the distal end of the outer sheath 465 at a first stop 469, as shownin the partial cross-sectional side view of FIG. 79A. A second stop 471may be positioned proximally of the first stop 469 which limits theproximal withdrawal of the linkage 475 by a predetermined distance. Whenthe linkage 475 engages the first stop 469 and retracts the sheathdistal end to radially extend the expandable portion 467, the furtherretraction of linkage 475 may be stopped by the second stop 471. Theouter sheath 465 may define the lumen through which the cooling probeassembly may be advanced without interference from the retractionassembly. Another variation is illustrated in FIG. 79B which shows asimilar mechanism but where the second stop 471 may be replaced by abiasing element 473, e.g., spring, positioned proximally of the firststop 469.

Yet another variation is shown in the side views of FIGS. 80A and 80Bwhich illustrate a representation of an exemplary overcenter linkagemechanism 481 which may be incorporated with the retraction mechanism. Alinkage 483 and corresponding biasing element 485, e.g., spring, may becoupled to the linkage member 475 attached to the stop 469. As thelinkage 475 is retracted to reconfigure the expandable portion 467, theovercenter mechanism 481 may also be retracted and actuated to engage aposition of the linkage 475 such that the retraction of the expandableportion 467 may be selectively maintained. The overcenter mechanism 481may be selectively disengaged to release and reconfigure the expandableportion 467.

FIG. 81 shows a side view of yet another variation where the outersheath 491 may incorporate one or more distal cam members 493A, 493B.With the outer sheath 491 positioned distally of the tubing 201, the cammembers 493A, 493B may be configured into a first collapsedconfiguration. As the outer sheath 491 is retracted relative to tubing201, the cam members 493A, 493B may pivot along outer sheath 491 whenurged by the outer surface of the tubing 201 and reconfigure into anexpanded configuration as indicated. The reconfigured expanded cammembers 493A, 493B may then be used as a stop for the outer sheath 491relative to the cervical tissue.

An example of the reconfigured cam members 493A, 493B used as a stop isillustrated in the exemplary cross-sectional side view of FIG. 82. Asindicated, as the outer sheath 491 is retracted and the cam members493A, 493B reconfigure, the outer sheath 491 may be further retracteduntil secured against the cervix CV. FIG. 83 shows another example wherethe outer sheath 501 having the distal tip cam members 503A, 503B may beconfigured to have a tapered distal end 505 to allow for the furtherpivoting of the cam members 503A, 503B during sheath retraction.

FIG. 84 shows an exemplary illustration of how the outer sheath 465 maybe deployed first and secured into position with, e.g., the expandableportion 467, placed into contact against the cervix CV. The coolingprobe assembly and collapsed balloon 174 may then be inserted throughthe outer sheath 465 at a later time and advanced into the uterus UT fortreatment. In this and any of the other variations described herein, aspracticable, the outer sheath may be deployed independently of thecooling probe if so desired.

FIG. 85 shows yet another variation where the outer sheath may beconfigured as a corrugated outer sheath 511 to provide a structure whichis strong yet flexible. FIGS. 86 and 87 show additional variations wherethe outer sheath 513 may comprise an annular balloon 517 located alonginner surface of sheath 513. The sheath distal end may define one ormore longitudinal slots 515 for selective expansion of the balloon 517.Alternatively, the annular balloon 519 may be located along outersurface of sheath 513, as also previously described.

FIGS. 88A to 88D show yet another variation where the sheath 521 mayincorporate an integrated feature to provide further insulation betweenthe cryoablative fluid and the surrounding cervical tissue by creatingor forming insulative pockets of air. The variation shown in thecross-sectional end view of FIG. 88A shows a sheath 521 defining aplurality of raised and curved surfaces 523 along the inner surface ofthe sheath 521. FIG. 88B shows another variation where a plurality ofraised and curved surfaces 525 may be formed along the outer surface ofthe sheath 521. Yet another example is shown in FIG. 88C which shows asheath 521 formed to have both internal and external raised surfaces 527while the variation of FIG. 88D shows a variation where the internalsheath surface may have a plurality of raised projections or fingersextending inwardly.

In controlling the ablative treatments described above, the treatmentassembly may be integrated into a single cooling system 420, as shown inthe exemplary schematic illustration of FIG. 89. The cooling system 420may be contained entirely within the handle assembly 214 as describedabove or it may be separated into components, as needed or desired. Ineither case, the cooling system 420 may generally comprise amicrocontroller 422 for monitoring and/or controlling parameters such ascavity temperature, cavity pressure, exhaust pressure, etc. A display424, e.g., a digital display which may be located along handle assembly214, may be in communication with the microcontroller 422 for displayingparameters such as cavity pressure, cavity temperature, treatment time,etc. Any errors may also be shown on the display 424 as well. A separateindicator 426, e.g., visual or auditory alarm, may also be incommunication with the microcontroller 422 for alerting the user toprompts, errors, etc. through as any number of indicators, symbols, ortext, etc., for alerts, as well as for instructions, or otherindications.

A coolant reservoir 428, e.g., nitrous oxide canister in this example,may be fluidly coupled to the handle 214 and/or elongate shaft 170 via acoolant valve 430 which may be optionally controlled by themicrocontroller 422. The coolant reservoir 428 may be in fluidcommunication with the cooling probe assembly 220 and with the interiorof the balloon 174. One or more pressure sensors 432 may be incommunication with a pressure lumen 434 contained within the coolingprobe assembly 220 or elongate shaft 170 and one or more temperaturesensors 436 in communication with a thermocouple/thermistor wire 438also contained within the cooling probe assembly 220 or elongate shaft170 may be incorporated. The one or more pressure sensors 432 and/ortemperature sensors 436 may be in communication with the microcontroller422 as well. Moreover, the pressure sensors 432 may optionally comprisea sensor positioned within the balloon 174 where the sensor is designedfor low temperature measurement. Such a pressure sensor may incorporatea closed or open column of liquid (e.g., ethanol, etc.) or gas (e.g.,air, carbon dioxide, etc.) which extends through the cooling probeassembly.

The cryoablative fluid contained within the coolant reservoir 428, suchas nitrous oxide, may be pumped (or allowed to flow if reservoir 428 isunder pressure) via, e.g., a motor-driven valve such as coolant valve430, to control nitrous oxide inflow rate. The valve 430 may also beused to maintain a desired amount of back pressure to separate the wallsof the uterus. For instance, a relatively low back pressure of, e.g., 40to 60 mm Hg, may be used. Alternatively, a simple but precise exhaustflow restriction might be all that is needed, e.g., such as a fixed,non-adjustable valve. In yet another alternative, vacuum pressure may beused to control the rate at which the exhaust gas is pulled-through,e.g., a nitrous oxide deactivation filter.

The rate at which the cryoablative fluid, such as the nitrous oxide, isdelivered may be controlled by the temperature measured within theballoon 174 and/or uterine cavity. The target temperature range mayrange, e.g., between −65 and −80 degrees C. By limiting the temperaturemeasured within the balloon 174 to a value which is lower than theboiling point of nitrous oxide, about −88.5 degrees C., the chance ofliquid nitrous oxide build-up in the balloon 174 may be greatly reducedto prevent any excessive intrauterine pressures if the exhaust tube isblocked.

In the event that excessive pressure is measured within the balloon 174or the pressure differential between two sensors is too large, thesystem may be programmed to automatically stop the flow of thecryoablative fluid. A separate shut-off valve may be used in-place ofthe coolant valve 430. Furthermore, if electrical power is interruptedto the system, the separate shut-off valve may automatically beactuated. In addition, the indicator 426 may signal to the user thatexcessive pressures were reached and the system shut-down.

The inside diameter of the delivery line may also be sized to delivercryoablative fluid up to but not exceeding, e.g., a maximum anticipatedrate for a large, well-perfuse uterus. By limiting the rate ofcryoablative fluid infusion and sizing the exhaust tube appropriately,the system may be able to evacuate the expanded gas even in the event ofa catastrophic failure of the delivery line.

Additionally, an exhaust lumen 440 in communication with the elongateprobe 170 and having a back pressure valve 444 may also include apressure sensor 442 where one or both of the back pressure sensor 442and/or valve 444 may also be in communication with the microcontroller422. While the microcontroller 422 may be used to control the pressureof the introduced cryoablative fluid, the pressure of the cryoablativefluid within the balloon 174 interior may also be controlledautomatically by the microcontroller 422 adjusting the back pressurevalve 444 or by manually adjusting the back pressure valve 444. In theevent that the microcontroller 422 is used to control the back pressurevia valve 444, the microcontroller 422 may be configured or otherwiseprogrammed to adjust the valve 444 based on feedback from other sensors,such as the measured parameters from the one or more pressure sensors432 and/or temperature sensors 436 to create a closed feedback loopsystem. A vacuum may also be optionally incorporated into the closedfeedback loop.

The exhaust lumen 440 may be fluidly connected, e.g., to a reservoir 446for collecting or deactivating the exhausted cryoablative fluid. Thereservoir 446 may optionally incorporate a filter into the handle 214 orbecome integrated into a reusable console. Alternatively, the exhaustedcryoablative fluid may be simply collected in a reservoir 446 orexhausted into atmosphere.

Generally, redundant pressure lines and sensors, such as pressure lumen434, that terminate in the balloon 174 may correspond to sensors locatedin the handle 214 to make comparison measurements. The pressure linesmay be filled with a fluid such as ethanol to prevent freezing during aprocedure. Alternatively, a gas such as air may be used in the pressurelines but may utilize temperature compensation.

As at least one thermocouple may be located within the balloon 174 andused to measure temperature during the procedure, additionalthermocouples may be optionally included at other locations internal orexternal to the balloon 174 to provide for additional temperaturemeasurements. For example, a thermocouple may be optionally located onthe distal portion of the sheath 212 to monitor temperature within thecervix CV.

After completion of the procedure, all unused cryoablative fluid stillcontained in the reservoir 428 or within the system may be automaticallyor manually vented, e.g., to the deactivation filter or collectionreservoir 446.

The system 420 may optionally further incorporate an emergency shut-offsystem which may be actuated in the event that electrical power is lost,if a user manually activates the shut-off system, or in the event thatthe microcontroller 422 detects a high-pressure within the system 420.One example of the emergency shut-off system may incorporate anemergency shut-off valve which may include valve 430 or which mayalternatively incorporate another valve separate from valve 430.Moreover, in detecting the pressure within the system 420, a redundantpressure sensor may also be utilized along with the one or more pressuresensors 432 either at the same location or at a different location alongthe system 420.

In any of the examples described herein, the system may employ athermally conductive fluid having a thermal conductivity greater thanthat of saline. This thermal conductivity may help to ensure that thefluid within the body cavity or lumen is at the same temperaturethroughout even without agitation or lavage. Such a fluid may be usedwith the fluid lavage and/or the fluid infusion followed by applicationof a cryoprobe. The improved thermal conductivity may be achieved via avariety of different options including, but not limited to, choice of athermally conductive fluid or gel, addition of thermally conductivecompounds to the fluid or gel (e.g., metals or metal ions, etc.) and/oragitation of the fluid within the cavity to help achieve equilibrationof the temperature. Additionally, the fluid may be infused as a fluid orgel until a set pressure is achieved. The cryoprobe may then beintroduced into the body cavity/lumen and heat may be withdrawn from thefluid/gel. Prior to or in concert with the achievement of acryotherapeutic (ablative or non-ablative) temperature, the fluid or mayform a gel or solid. This may be utilized such that fluid or gel withinthe cavity may be trapped within the target lumen or body cavity withits change in viscosity or state thereby preventing leakage of the fluidor gel and unwanted exposure of adjacent tissues to the cryotherapeuticeffect. Due to the higher thermal conductivity or the gelled or frozenfluid or gel, the continued removal of heat from the gelled or frozenmass may be rapidly and uniformly distributed throughout the body cavityor lumen. The solution may also be partially frozen or gelled and thenagitated or recirculated to ensure even greater distribution of thecryotherapeutic effect. Moreover, the fluid may also be formulated tohave a freezing temperature at the desired ablation temperature suchthat the fluid remains at the desired ablation temperature for asignificant amount of time while the fluid changed from a liquid to asolid or vice versa.

Furthermore, the fluid or gel may be made thermally conductive by theaddition of a biocompatible metal or metallic ion. Any metal orconductive material may be used for this purpose, e.g., silver, gold,platinum, titanium, stainless steel, or other metals which arebiocompatible. Alternatively the thermally conductive fluid may be usedto transmit the thermal energy to tissues in order to provide thermalablation as opposed to the extraction of energy with cryoablation. Ineither embodiment, with sufficient thermal conductivity the fluid mayact as an extension of the ablative energy source and provide a customablation tip for the application of or removal of energy from any bodytissues, body cavities, or body lumens. Another benefit is consistencyof treatment since cryoablation may require use of ultrasound in thesetting of uterine ablation. Any of the devices herein may allow for theuse of temperature tracking or simple timed treatment in order toautomate the ablation (with or without ultrasound monitoring). Forexample, application of −80 C. for 3 minutes has been shown to providethe correct depth of ablation for many uterine cavities. The devicesherein may allow for the tracking of temperature such that once adesired temperature is reached (e.g., −60 C.) a timer may be triggeredwhich automatically discontinues therapy and warms the cavity based ontime alone. This may be used in the setting of a fixed volume infusion(e.g., 10 to 15 cc of thermally conductive fluid/gel for all patients)or in the setting of infusion of a fluid/gel to a set pressure (withvariable volumes). This timed ablation may also be used in concert withany of the device herein to allow for elimination of the burdensomerequirement for ultrasound tracking of the cryogenically treatedregions.

Alternatively, this thermally conducting fluid (which may optionallyinclude solid particles of metal) may be infused into a balloon whichconforms to the uterus, esophagus or other body cavity or lumen atrelatively low pressures (e.g., less than 150 mmHg), as also describedabove. The thermally conducting material may alternatively be comprisedentirely of a solid (e.g., copper spheres or a copper chain) within theconforming balloon wherein the thermally conductive solid and/or fluidmay be reversibly delivered into the conforming balloon under lowpressure after which a cryoprobe, cryogenic liquid and/or cryogenic gasmay be delivered into the balloon and activated to ablate the entiretyof the uterus UT at once. The cryogen source may also be positionedwithin the balloon to obtain maximum cryoablation within the body ofuterus with less ablative effect proximally and in the cornua. Vaseline,oils or other thermally resistive materials may also be used inconjunction with this or other modalities in order to protect certainareas of the uterus, cervix and vagina.

In creating the optimal thermally conductive fluid and/or gel, anyconductive material may be added to the fluid or gel including, e.g.,gold, silver, platinum, steel, iron, titanium, copper or any otherconductive metal, ion, or molecule. If a metal is used as a dopant toincrease the thermal conductivity, the added metal may take any shape orform including spheres, rods, powder, nanofibers, nanotubes,nanospheres, thin filaments or any other shape that may be suspended ina solution or gel. The fluid or gel may itself also be thermallyconductive and may be infused and then removed or may be left in thecavity and allowed to flow naturally from the uterus as with normalmenstruation. The thermally conductive polymer may also bebiocompatible, as well, but this may not be necessary if the fluid/gelis extracted immediately following the procedure.

Despite the potential for toxicity, ethanol may be well suited for aliquid lavage in that it resists freezing down to −110 C. and is, otherthan dose dependent toxicity, biocompatible. Solutions of 75% to 99.9%ethanol concentrations may be used to good effect and have beendemonstrated to show that a freeze layer develops very rapidlyinhibiting further ethanol absorption. An ethanol copper composition mayalso be used since ethanol resists freezing whereas aqueous fluidsfreeze and expand thereby moving the metal particle out of directcontact with the tissue.

In another variation for creating back pressure within the system, FIGS.90A and 90B show a device for closing the exhaust flow path tofacilitate a liner integrity check and to also increase the pressurewithin the uterine cavity. As the liner is initially expanded (e.g., upto 100 mmHg of pressure), the transition between initial expansion andtreatment should desirably occur with a minimal change in cavitypressure. Hence, the pressure within the liner and system during thefirst 30 seconds of treatment is ideally maintained 85+/−15 mmHg. Thevariation shown in FIG. 90A illustrates an end cap 450 which may be usedto cover or obstruct the exhaust line 213 to facilitate the increase inback pressure during the initial expansion. The end cap 450 may contactthe exhaust tube contact 452 over the exhaust line 213 such that the endcap 450 and exhaust tube contact 452 are electrically coupled to form acircuit via conductive lines 454.

Once sufficient back pressure has been created in the system andcryoablation treatment is ready to begin, the end cap 450 may be removedfrom the exhaust tube contact 452 (manually or automatically) breakingthe electrical connection, as shown in FIG. 90B. The processor ormicrocontroller in the system may detect the electrical break andautomatically initiate infusion of the cryoablative fluid or gas tobegin the treatment. Moreover, because the exhaust line 213 is nowunobstructed, the discharged fluid or gas may also be vented or removedfrom the system through exhaust line 213.

In other variations for maintaining exhaust back pressure within thesystem, the pump (with or without a filter) may be used to increase thepressure. Alternatively, a compressed gas (e.g., coupled via a bladder,tank, etc.) may be infused into the liner and system to increase thepressure. In either case, any of these methods may be used in variouscombinations with any of the system or device variations describedherein.

Alternative mechanisms may also be used for maintaining a sufficientback pressure within the system and the liner. Another variation isshown in the schematic side view of FIG. 91A of flapper valve 460 suchas an electromechanical flapper valve which may be incorporated withinthe handle assembly 211 (e.g., positioned between the pump and theliner) for fluidly coupling to the liner and exhaust. FIG. 91illustratively shows flapper valve 460 having a chamber 462 with atranslating piston 464 within the chamber 462. The pump 468 may befluidly coupled via pump line 470 to the first section 480 of thechamber 462 (e.g., at a top of the chamber 462) and exhaust and/or linerchannel 472 may also be similarly fluidly coupled to the first section480 of chamber 462. The exhaust and/or liner channel 472 may alsoincorporate a unidirectional valve 474 within the channel 472 such thatfluid or gas may pass through channel 472 and past unidirectional valve474 but is prevented from flowing back into first chamber 480.

The exhaust and/or liner channel 476 may be fluidly coupled to thesecond section 482 of chamber 462 (e.g., at the bottom of the chamber462) in proximity to ambient line 478. A sealing gasket 466 having afirst sealing ring 466A which encircles the periphery of the chamber 462and a second sealing ring 466B which encircles the entry to the exhaustand/or liner channel 476 may also be incorporated in the second chamber482, as shown in the top view of FIG. 91B.

The flapper valve 460 may remain closed by the system (e.g., motor,linear actuator, magnetic, electromagnetically, etc.) but opened by thesystem as the ablation treatment begins. The flapper valve may beactuated, e.g., by a separate button or actuator, positioned upon thehandle assembly 211.

When actuated, the pump 468 may be turned on and the piston 464 mayremain positioned at the bottom of the chamber 462 upon the sealinggasket 466, as shown in the side view of FIG. 91C. The piston 464 mayform a moderate seal while sitting upon the gasket 466 but as thepressure in the chamber 462 is increased, the sealing between the piston464 and gasket 466 may be increased accordingly. The gasket 466 itselfmay form different regions of relatively low pressure in the areabetween the first sealing ring 466A and the second sealing ring 466B(e.g., at atmospheric pressure) and high pressure in the area surroundedby the second sealing ring 466B (e.g., at the same pressure as withinthe liner/exhaust) during the initial pump up phase.

After the liner has been pumped up to its pre-determined pressure levelto properly distend the cavity and deploy the liner (e.g., 85 mmHg), thepump 468 may be reversed to remove the pressure from the chamber 462.The one-way or uni-directional valve 474 may prevent the vacuum frompulling on the liner as would the seal at the bottom of the chamber 462formed by the piston 464.

When P2 is lowered, the force of P1 upon the bottom of the piston 464may cause it to lift within the chamber 462, as shown in FIG. 91D. Thispiston movement will cause P1 to drop as the seal at the bottom breaksand as P1 begins to drop, the vacuum may shut off and the treatment maybe initiated. The flow of the cryogenic fluid or gas through the chamber462 may cause the piston 464 to move to the top of the chamber 462 whichmay allow for the free flow of nitrous to the environment, as shown inFIG. 91E.

FIGS. 92A and 92B show an alternative flapper valve 490 which mayfunction similarly except for the pump/vacuum line 470 may be positionedalong a side wall of the chamber 462. With the vacuum/pump line 470 sopositioned, the line 470 may remain below the piston 464 while thecryogenic fluid or gas flows through the chamber 462, as shown in FIG.92B. If the back pressure in the system is too high, the pump or avacuum pump 468 may be actuated to provide a slightly negative pressureor suction that may lower the back pressure on the system.

As previously described, the system may be programmed to enable a numberof different processes. The processor or microcontroller may beaccordingly programmed with a number of different algorithms dependingon the functional mode to be performed. FIG. 93 illustrates how thedifferent algorithms 500 may be programmed into the processor ormicrocontroller and how they may functionally interact with one another.Once the device is initially powered on, the system may enter a Start-UpMode 502 where the system performs a self-check of the sensors and theoverall system. Some of the checks may include, e.g., ensuring pressuresensors have a detected initial reading of between 0 and 10 mmHg whichdo not deviate from one another by more than 5 mmHg; detecting a batteryvoltage reading of greater than 7.5 V; and/or detecting any memoryfeature which may be used to record various readings and parameters aswell as load any number of additional features into the system.

Once the Start-Up Mode 502 has been initiated and/or completed, the usermay, e.g., actuate the system to enter a Liner Puff Mode 504. In LinerPuff Mode 504, the system may slowly add ambient filtered air into theliner until target treatment pressure is reached, as described above.The pump may be turned on until the pressure has increased by, e.g., 5mmHg, and may then be shutoff for, e.g., 2 seconds. The pump may cycleon and off until the system measures, e.g., 85 mmHg. Typically, the fullramp-up may take, e.g., 15-20 seconds. When 85 mmHg is reached, thedevice may then enter Liner Check Mode 506. In this mode, the system maydetect for leaks in the system. The system may waits for, e.g., 5seconds, after Liner Puff Mode 504 is complete and then detect whetherthe pressure is still above, e.g., 40 mmHg or more. If the system isholding pressure, the device may then enter Treat Mode 508.

During Treat Mode 508, the system may deliver the cryogenic fluid or gasto the liner while looking for pressure faults. An example of a pressurefault may include a detected pressure value greater than, e.g., 150mmHg. The treatment may be stopped automatically and user restart may behalted at least temporarily by the system. Another example of a pressurefault may include when a detected pressure deviates from other pressurereadings by, e.g., 20 mmHg or greater for 3 consecutive seconds. Again,treatment may be stopped automatically and user restart may be halted atleast temporarily by the system. Once a predetermined time period haselapsed, e.g., 2 minutes and 30 seconds, the device may enter Thaw Mode510.

In Thaw Mode 510, the system may push puffs of ambient filtered air intothe liner to warm it up for removal from the patient. The pump may pushair into the cavity while the exhaust solenoid is closed until, e.g., 10mmHg pressure in the cavity is measured. The pump may be then turned offand the exhaust solenoid opened for, e.g., 2 seconds to allow the air toescape the cavity. The pump/open cycle may be repeated for, e.g., 2minutes. Additionally and/or optionally, a vacuum may also be used inThaw Mode 510, e.g., to facilitate peeling of the liner 174 from thefrozen uterine walls and to expedite the removal of the device.

Once Thaw Mode 510 has been completed, the system may then enterDisposal Mode 512 where the liner and system may be evacuated of anycryogenic fluid or gas. In the event that any of the different modesdetects a failure, e.g., if the Startup Mode 502 fails, too many puffattempts are detected during the Liner Puff Mode 504, a leak is detectedduring the Liner Check Mode 506, or a pressure fault is detected by thesystem during the Treat Mode 508, then the system may automaticallydefault into entering the Disposal Mode 512.

In the event that the user pauses the system anytime during the LinerPuff Mode 504 or the Liner Check Mode 506, the system may enter into thePause Mode 514 where the system releases pressure and waits indefinitelyfor the user to re-initiate the puff up sequence by initiating thesystem again. In the event that the user pauses the system anytimeduring the Treat Mode 508, the user may have a predetermined period oftime, e.g., 15 seconds, to re-start treatment or the system may stopentirely. The time limit may be imposed so that the frozen tissue doesnot thaw significantly which could affect the ultimate depth ofablation. When treatment is re-started, the treatment time resumes fromwhere it was paused.

Additionally and/or optionally, the processor or microcontroller mayalso be programmed to monitor the overall system. Hence, the system maybe programmed to transmit a signal on a regular basis, e.g., everysecond, to a monitoring system. If the monitoring system fails toreceive the signal, the entire system may be shut down such that thevalves automatically close, the exhaust valve opens, and the pumps shutdown.

Additional features may also be incorporated for safety. For instance,in order to prevent high pressure from developing within the uterus dueto the accumulation of the cryogenic fluid or gas, safety features maybe integrated into the system. Examples of some of the safety featuresmay include: redundant, kink-resistant pressure lines and sensors tomonitor intrauterine cavity pressure; flow rate-limited delivery line tominimize the amount of cryogenic fluid or gas introduced into the cavityin the event of a catastrophic failure; pressure relief valve in theexhaust flow path which opens if the primary path is obstructed;flexible yet crush-resistant, laser-cut, stainless steel exhaust tubewithin the liner; fail-safe solenoid valve on the cryogenic fluid or gasinflow path which closes in the event of a power failure or othercontrol system failure; and/or software watchdog to safely shutdown thedevice in the event of a software malfunction.

Moreover, in order to prevent cryogenic fluid or gas in the exhaust fromcoming into contact with the physician or patient, additional safetyprovisions may also be implemented. Examples of some of these safetyprovisions may include: heat sink in the exhaust pathway to promote theconversion of cryogenic fluid or gas from liquid to gaseous states;and/or convoluted tube at the end of the exhaust path to further promotecryogenic fluid conversion from liquid to gaseous states and alsoprevent cryogenic fluid or gas from contacting the physician or patient.

As described herein, various visualization modalities may be utilizedwith any of the system variations described. For instance, hysteroscopicvisualization may be accomplished by utilizing scope having, e.g., a 2.9mm outer diameter and 39 cm length. Such a scope may be introducedthrough, e.g., the handle assembly 211, through a seal that interfaceswith the scope and allows for the inflation of the liner with the scopein place if a more broad view of the cavity is desired. The scope may beremoved before treatment is initiated.

Additionally and/or alternatively, ultrasound visualization may also beutilized to aid the user in the placement of the device within thecavity. During treatment, the cryogenic fluid or gas is visible underultrasound as is the ice front.

While the treatment assembly may be comprised of a completely disposablehandheld device which is provided sterile to the user, the cryogenicfluid or gas, e.g., liquid N₂O, may be contained in a canister which isintegrated into the device. Alternatively, the assembly may be tetheredto a reusable liquid N₂O tank. Electronic components may be relocatedfrom the handheld device to a reusable console which could also containthe liquid N₂O tank. In another alternative, a simple disposable elementof the system may attach to a reusable handle tethered to a liquid N₂Otank. The reusable handle could be re-sterilizable and may contain themajority of the components normally contained within the disposablehandle. The disposable element could consist of the flexible probe,liner, pressure-sensing lumens and the N₂O delivery line.

While the system is described above for the cryoablative treatment ofthe uterine cavity, the system may also be used for other applications.For instance, the system may be utilized for shrinking or killinguterine fibroids where the probe may be inserted and the liner inflatedwith gas, as previously described, and a visualization element(ultrasound or hysteroscopy) may be used to position a freezing elementup against the fibroid and freezing may be initiated. The freezingelement may be positioned against the endometrial wall or may beinserted into the fibroid itself. The time of the freeze may bedetermined based upon the size of the fibroid with longer freezes forlarger fibroids.

In addition to the initial positioning, the freeze may also be trackedusing ultrasound, hysteroscopy or other visualization tools and stoppedonce a sufficient freeze has been achieved. The cryogen may be infusedinto a small balloon or liner inflated within the larger, gas-filledliner which may extract energy across both liners from the fibroid. Thecryogen transmitting lumen can also be flexibly directed to the surfaceof the fibroid under visualization and the cryogen transmission ballooncan be sized to best fit the endometrial surface of the fibroid and thefreeze can be initiated and tracked under visualization. The smallcryogen transmission balloon may also be replaced with a metal or otherthermally conductive tip in which the cryogen undergoes a phase changeand/or extracts energy. The gas-filled liner will allow for goodvisualization of the uterus and the freezing probe. In alternativevariations, hyperthermal or other destructive energy may also betransmitted across the liner in order to destroy the fibroid with theliner simply acting as a source of controlled visualization without theintroduction of saline or other distention media.

In yet another application, the system may be used to treat conditionssuch as Barrett's Esophagus. The probe may be inserted under endoscopicvisualization and the liner sized to the length of the esophagus to betreated. The liner may then be inflated and visualization may berepeated across the liner to ensure optimal distention and contact withtissues to be treated. The cryogen delivery probe may then deliver aliquid cryogen or, preferably, a cold gas to the interior of the linerto treat the tissues adjacent to the liner. If needed or desired, theliner may then be deflated, repositioned and cryogen may be reinfusedone or more times. This may be particularly the case for a relativelysmaller esophagus in which the oversized liner may have more extremefolds which could prevent energy transmission. Repositioning andredeployment of the liner may allow for these folds to occur indifferent areas and will allow for a more consistent ablation. The useof cold gas may also allow for a more consistent, light ablation, aswell, due to the smaller gradient in temperature and lack of thepowerful phase change. Benefits of this design include the ability toprevent overlapping circumferential ablations which have been found tocause strictures and stenosis. Additional benefit can be found from theconsistent treatment of all or part of the esophagus, including thegastroesophageal junction.

In yet another application, the system may be used to treat conditionssuch as treating benign prostatic hyperplasia (BPH) by shrinking theprostrate. The prostate tissue is sensitive to cryotherapy as evidencedby the efficacy of cryogenic freezing of the prostate for oncology. Inthis variation of the device, the liner may be placed in the urethra inthe region of the prostate and cryogen may be infused (liquid or gas)into the liner. The energy may be transmitted across the wall of theliner and the urethra into the prostate causing apoptosis and death ofthe prostatic cells that are generating the symptoms of benign prostatichyperplasia. The urethra may be temporarily stented open to allow forepithelialization without stricture formation either before or after thetherapy. The stent could be configured to degrade over time, pass on itsown and provide symptomatic relief and protection from urine during thehealing period (i.e., be an occlusive barrier).

Due to the ease of visualization of the freeze, this therapy may also beconducted under direct visualization to ensure optimal freezing. Thisfreeze may be stopped and/or restarted by the user, but may optimally bea programmed time or time at temperature. The therapy may also beperformed without visualization in which case the freeze probe may beinserted with a location indicator (i.e., a balloon that is inflated inthe bladder and drawn back to the urethral outlet) and therapy initiatedonce the correct position has been obtained.

While illustrative examples are described above, it will be apparent toone skilled in the art that various changes and modifications may bemade therein. Moreover, various apparatus or procedures described aboveare also intended to be utilized in combination with one another, aspracticable. The appended claims are intended to cover all such changesand modifications that fall within the true spirit and scope of theinvention.

What is claimed is:
 1. A tissue treatment system, comprising: a handlehaving a housing; an elongate probe extending from the housing andhaving a distal tip and a flexible length; a liner expandably enclosingthe probe; at least one infusion lumen positioned through or along theelongate probe, wherein the infusion lumen defines one or more openingsalong its length; at least one delivery lumen slidingly positionedthrough or along the infusion lumen, wherein proximal retraction of thedelivery lumen relative to the infusion lumen from a first locationincreases the number of unobstructed openings, and distal translation ofthe delivery lumen relative to the infusion lumen from the firstlocation decreases the number of unobstructed openings; and a controllerwhich is programmed to infuse ambient air into the interior of theliner, and wherein the controller is further programmed to infuse acryoablative fluid or gas into an interior of the liner via the infusionlumen for a period of time of up to 150 seconds such that thecryoablative fluid or gas is sprayed within the liner and into contactupon an interior surface of the liner.
 2. The system of claim 1 whereinthe ambient air is infused into the interior of the liner at a pressureof up to 85 mmHg and for a period of time of up to 20 seconds prior toinfusing the cryoablative fluid or gas.
 3. The system of claim 1 whereinthe controller is further programmed to detect whether the pressurewithin the interior of the liner remains above 40 mmHg over a period of5 seconds to determine whether a leak is present within the liner. 4.The system of claim 1 wherein the controller is further programmed todetect whether the pressure within the interior of the liner deviates by20 mmHg or more over a period of 3 seconds to determine whether a leakis present within the liner.
 5. The system of claim 1 wherein thecontroller is further programmed to infuse the cryoablative fluid or gasuntil a temperature of the interior of the liner is about −89° C.
 6. Thesystem of claim 1 wherein the controller is further programmed to ceaseinfusing the cryoablative fluid or gas into the interior of the liner.7. The system of claim 6 wherein the controller is further programmed toinfuse air into the interior of the liner at a pressure of about 10 mmHgwhile the cryoablative fluid or gas remains within the interior and thenvent for about 2 seconds to thaw tissue in contact with an exterior ofthe liner.
 8. The system of claim 1 wherein the elongate probe definesan exhaust lumen for an ablative fluid.
 9. The system of claim 1 whereinthe one or more openings along the infusion lumen are defined oppositeto one another along the infusion lumen.
 10. The system of claim 1further comprising a reservoir of a cryoablative fluid in fluidcommunication with the delivery lumen.
 11. The system of claim 10wherein the cryoablative fluid comprises nitrous oxide or argon.
 12. Thesystem of claim 1 further comprising a pump in fluid communication withthe liner interior.
 13. A method of treating tissue, comprising:positioning an elongate probe into a body lumen to be treated; infusingambient air into an interior of a liner enclosing the probe to expandthe liner into contact against the body lumen; adjusting a position of adelivery lumen relative to an infusion lumen which is positioned throughor along the elongate probe such that one or more openings defined alonga length of the infusion lumen are unobstructed, where proximalretraction of the delivery lumen relative to the infusion lumen from afirst location increases the number of unobstructed openings, and distaltranslation of the delivery lumen relative to the infusion lumen fromthe first location decreases the number of unobstructed openings;infusing a cryoablative fluid or gas through the delivery lumen suchthat the fluid passes into the infusion lumen, through the unobstructedopenings, and is sprayed into contact against the interior of the linerfor a period of time of up to 150 seconds such that the body lumen isablated.
 14. The method of claim 13 wherein the infusion of thecryoablative fluid or gas is controlled via a controller.
 15. The methodof claim 13 further comprising ceasing the infusion of the cryoablativefluid or gas into the interior of the liner.
 16. The method of claim 15wherein the ambient air is infused into the interior of the liner at apressure of up to 85 mmHg and for a period of time of up to 20 seconds.17. The method of claim 13 further comprising detecting whether thepressure within the interior of the liner remains above 40 mmHg over aperiod of 5 seconds to determine whether a leak is present within theliner.
 18. The method of claim 13 further comprising detecting whetherthe pressure within the interior of the liner deviates by 20 mmHg ormore over a period of 3 seconds to determine whether a leak is presentwithin the liner.
 19. The method of claim 13 wherein infusing acryoablative fluid or gas comprises infusing until a temperature of theinterior of the liner is about −89° C.
 20. The method of claim 13further comprising infusing air into the interior of the liner at apressure of about 10 mmHg while the cryoablative fluid or gas remainswithin the interior and then venting for about 2 seconds to thaw tissuein contact with an exterior of the liner.